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Xu C, Zhu R, Dai Q, Li Y, Hu G, Tao K, Xu Y, Xu G, Zhang G. TIMP-2 Modulates 5-Fu Resistance in Colorectal Cancer Through Regulating JAK-STAT Signalling Pathway. J Cell Mol Med 2025; 29:e70470. [PMID: 40118773 PMCID: PMC11928231 DOI: 10.1111/jcmm.70470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 01/26/2025] [Accepted: 02/21/2025] [Indexed: 03/23/2025] Open
Abstract
The main reason for the failure of chemotherapy therapies based on 5-Fluorouracil (5-Fu) is the development of resistance to 5-Fu in cancer patients, particularly those with colorectal cancer. Tissue inhibitor of metalloproteinases 2 (TIMP-2) has been shown to be associated with colorectal cancer (CRC), but its correlation with 5-Fu resistance in colorectal cancer has not been thoroughly studied. We screen the expression of different cytokines through Cytokine array. CCK-8 assay was conducted to evaluate the IC50 of 5-Fu and cell proliferation. ELISA and RT-qPCR were performed to detect TIMP-2 expression levels in cells and patient serum. Western blotting was utilised to analyse the differences in the expression of proteins related to signalling pathways in cells. Through cytokine array screening, we found that the expression of TIMP-2 was significantly increased in CRC drug-resistant cell lines. In addition, the expression of TIMP-2 in the serum of patients with CRC resistance to 5-Fu was significantly increased. Subsequent mechanistic experiments showed that TIMP-2 regulated the resistance of CRC cells to 5-Futhrough the JAK-STAT signalling pathway. Moreover, anti-TIMP-2 antibody or small molecule drug LY2784544 targeting the JAK-STAT signalling pathway can effectively reverse the resistance of CRC cells to 5-Fu. It is exactly TIMP-2 that mediates the resistance of CRC to 5-Fu through the JAK-STAT signalling pathway. Targeting drugs for TIMP-2 or the JAK-STAT signalling pathway are expected to be opportunities to reverse 5-Fu resistance in CRC.
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Affiliation(s)
- Chuchu Xu
- Department of Gastrointestinal SurgeryShaoxing People's HospitalShaoxingZhejiang ProvinceChina
| | - Renjun Zhu
- Department of EmergencyShaoxing People's HospitalShaoxingZhejiang ProvinceChina
| | - Qingfeng Dai
- Zhijiang College, Zhejiang University of TechnologShaoxingZhejiang ProvinceChina
| | - Yaoqing Li
- Department of Gastrointestinal SurgeryShaoxing People's HospitalShaoxingZhejiang ProvinceChina
| | - Gengyuan Hu
- Department of Gastrointestinal SurgeryShaoxing People's HospitalShaoxingZhejiang ProvinceChina
| | - Kelong Tao
- Department of Gastrointestinal SurgeryShaoxing People's HospitalShaoxingZhejiang ProvinceChina
| | - Yuhong Xu
- Department of GynaecologyShaoxing People's HospitalShaoxingZhejiang ProvinceChina
| | - Guangen Xu
- Department of Gastrointestinal SurgeryShaoxing People's HospitalShaoxingZhejiang ProvinceChina
| | - Guolin Zhang
- Department of Gastrointestinal SurgeryShaoxing People's HospitalShaoxingZhejiang ProvinceChina
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Chen Y, Chen B, Tu S, Yuan H. miR‑25‑3p serves as an oncogenic in colorectal cancer cells by regulating the ubiquitin ligase FBXW7 function. Oncol Rep 2024; 52:153. [PMID: 39329268 PMCID: PMC11450686 DOI: 10.3892/or.2024.8812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 06/12/2024] [Indexed: 09/28/2024] Open
Abstract
Accumulating evidence indicates that the dysregulation of microRNAs (miRNAs or miRs), is associated with human malignancies and suggests a casual role of miRNAs in tumor initiation and progression. Even though it has been discovered that a number of miRNAs play significant parts in the development of colorectal cancer (CRC), it is crucial to comprehend the regulatory functions that other miRNAs play in CRC. Based on GSE183437 and GSE156719 microarray data that were obtained from Gene Expression Omnibus database, candidate miRNAs were researched. The oncogenic effects of miR‑25‑3p in different malignancies have led to its selection for additional investigation in the present study. The expression of miR‑25‑3p was verified by reverse transcription‑quantitative PCR, and its correlation with clinicopathological characteristics in patients with CRC was then investigated. In vitro assays were conducted to investigate the influence of miR‑25‑3p on the proliferative and apoptotic behaviors of HCT116 and Caco‑2 cells. The present data revealed that miR‑25‑3p exhibited one of the most significant upregulations in CRC tissues and cell lines. The expression levels of miR‑25‑3p were found to be intimately correlated with tumor size, distant metastasis, tumor‑node‑metastasis stage, and shorter overall survival rate. In terms of functionality, the downregulation of miR‑25‑3p led to the inhibition of cellular proliferation and the enhancement of apoptosis in both HCT116 and Caco‑2 cell lines. The critical tumor suppressor F‑box and WD repeat containing domain 7 (FBXW7) was identified as a direct molecular target for miR‑25‑3p, with an inverse relationship observed between the two in neoplastic tissues. Subsequent studies demonstrated that the tumor suppressive effects of miR‑25‑3p inhibitor were effectively negated by the silencing of FBXW7. Moreover, the ability of FBXW7 to inhibit the expression of several oncogenes was deemed essential for countering the anticancer effects mediated by miR‑25‑3p downregulation. These findings posit miR‑25‑3p as a promising therapeutic target and prognostic indicator for CRC.
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Affiliation(s)
- Yanbin Chen
- General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Bingchen Chen
- General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Shiliang Tu
- General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Hang Yuan
- General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
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Fahmy SA, Mahdy NK, Mohamed AH, Mokhtar FA, Youness RA. Hijacking 5-Fluorouracil Chemoresistance in Triple Negative Breast Cancer via microRNAs-Loaded Chitosan Nanoparticles. Int J Mol Sci 2024; 25:2070. [PMID: 38396746 PMCID: PMC10889139 DOI: 10.3390/ijms25042070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 01/26/2024] [Accepted: 02/07/2024] [Indexed: 02/25/2024] Open
Abstract
Chemotherapy is still the mainstay of treatment for triple-negative breast cancer (TNBC) patients. Yet only 20% of TNBC patients show a pathologic complete response (pCR) after neoadjuvant chemotherapy. 5-Fluorouracil (5-FU) is a stable cornerstone in all recommended chemotherapeutic protocols for TNBC patients. However, TNBC patients' innate or acquired chemoresistance rate for 5-FU is steeply escalating. This study aims to unravel the mechanism behind the chemoresistance of 5-FU in the aggressive TNBC cell line, MDA-MB-231 cells, to explore further the role of the tumor suppressor microRNAs (miRNAs), miR-1275, miR-615-5p, and Let-7i, in relieving the 5-FU chemoresistance in TNBC, and to finally provide a translational therapeutic approach to co-deliver 5-FU and the respective miRNA oligonucleotides using chitosan-based nanoparticles (CsNPs). In this regard, cellular viability and proliferation were investigated using MTT and BrdU assays, respectively. 5-FU was found to induce JAK/STAT and PI3K/Akt/mTOR pathways in MDA-MB-231 cells with contaminant repression of their upstream regulators miR-1275, miR-615-5p, and Let-7i. Moreover, CsNPs prepared using the ionic gelation method were chosen and studied as nanovectors of 5-FU and a combination of miRNA oligonucleotides targeting TNBC. The average particle sizes, surface charges, and morphologies of the different CsNPs were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. In addition, the encapsulation efficiency (EE%), drug loading capacity (DLC%), and release manner at two different pH values were assessed. In conclusion, the novel CsNPs co-loaded with 5-FU and the combination of the three miRNA oligonucleotides demonstrated synergistic activity and remarkable repression in cellular viability and proliferation of TNBC cells through alleviating the chemoresistance to 5-FU.
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Affiliation(s)
- Sherif Ashraf Fahmy
- Chemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo 11835, Egypt
| | - Noha Khalil Mahdy
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt
| | - Adham H Mohamed
- Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), New Administrative Capital, Cairo 11835, Egypt
- Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
| | - Fatma A Mokhtar
- Fujairah Research Centre, Sakamkam Road, Fujairah 1626, United Arab Emirates
- Department of Pharmacognosy, Faculty of Pharmacy, El Saleheya El Gadida University, El Saleheya El Gadida 44813, Sharkia, Egypt
| | - Rana A Youness
- Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), New Administrative Capital, Cairo 11835, Egypt
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Wang J, Jia Q, Jiang S, Lu W, Ning H. POU6F1 promotes ferroptosis by increasing lncRNA-CASC2 transcription to regulate SOCS2/SLC7A11 signaling in gastric cancer. Cell Biol Toxicol 2024; 40:3. [PMID: 38267746 PMCID: PMC10808632 DOI: 10.1007/s10565-024-09843-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/22/2023] [Indexed: 01/26/2024]
Abstract
OBJECTIVE This study investigated the effect and mechanism of POU6F1 and lncRNA-CASC2 on ferroptosis of gastric cancer (GC) cells. METHODS GC cells treated with erastin and RSL3 were detected for ferroptosis, reactive oxygen species (ROS) level, and cell viability. The expression levels of POU6F1, lncRNA-CASC2, SOCS2, and ferroptosis-related molecules (GPX4 and SLC7A11) were also measured. The regulations among POU6F1, lncRNA-CASC2, FMR1, SOCS2, and SLC7A11 were determined. Subcutaneous tumor models were established, in which the expressions of Ki-67, SOCS2, and GPX4 were detected by immunohistochemistry. RESULTS GC patients with decreased expressions of POU6F1 and lncRNA-CASC2 had lower survival rate. Overexpression of POU6F1 or lncRNA-CASC2 decreased cell proliferation and GSH levels in GC cells, in addition to increasing total iron, Fe2+, MDA, and ROS levels. POU6F1 directly binds to the lncRNA-CASC2 promoter to promote its transcription. LncRNA-CASC2 can target FMR1 and increase SOCS2 mRNA stability to promote SLC7A11 ubiquitination degradation and activate ferroptosis signaling. Knockdown of SOCS2 inhibited the ferroptosis sensitivity of GC cells and reversed the effects of POU6F1 and lncRNA-CASC2 overexpression on ferroptosis in GC cells. CONCLUSION Transcription factor POU6F1 binds directly to the lncRNA-CASC2 promoter to promote its expression, while upregulated lncRNA-CASC2 increases SOCS2 stability and expression by targeting FMR1, thereby inhibiting SLC7A11 signaling to promote ferroptosis in GC cells and inhibit GC progression.
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Affiliation(s)
- Jingyun Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China
| | - Qiaoyu Jia
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China
| | - Shuqin Jiang
- Department of Child Development and Behavior, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People's Republic of China
| | - Wenquan Lu
- Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, No.2 JingBa Road, Jinshui District, Zhengzhou, Henan, 450014, People's Republic of China
| | - Hanbing Ning
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Erqi District, Zhengzhou, Henan, 450000, People's Republic of China.
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Rahbar Farzam O, Najafi S, Amini M, Rahimi Z, Dabbaghipour R, Zohdi O, Asemani Shahgoli G, Baradaran B, Akbari B. Interplay of miRNAs and lncRNAs in STAT3 signaling pathway in colorectal cancer progression. Cancer Cell Int 2024; 24:16. [PMID: 38185635 PMCID: PMC10771635 DOI: 10.1186/s12935-023-03202-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 12/27/2023] [Indexed: 01/09/2024] Open
Abstract
In recent decades, colorectal cancer (CRC) has turned into one of the most widespread malignancies, and the incidence of this malignancy is expected to increase. Despite considerable improvements in therapeutic approaches, the prognosis, and the management of CRC face many problems. Likely, the main limitation in the successful treatment of CRC is the lack of appropriate clinical therapeutic targets. As an effective target, the signal transducer and activator of transcription 3 (STAT3) are regulated by a wide range of genes and involved in cellular processes, including cell growth, migration, invasion, immunosuppression, and angiogenesis. Aberrant regulation of STAT3 signaling leads to cellular dysfunction, diseases, and malignancies, including CRC. Consequently, targeting this signaling pathway is considered one of the therapeutic strategies used in CRC treatment. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are non-coding RNA molecules with partial or no protein-coding activity that participate in gene regulation at epigenetic, transcriptional, and post-transcriptional levels and regulate multiple signaling pathways, including STAT3 signaling (especially JAK/STAT). Therefore, these regulatory molecules are suggested to be very promising targets to present new insights into overcoming the limitations of conventional therapeutic strategies. Therefore, the current review study aimed to summarize the therapeutic and diagnostic significance of miRNAs and lncRNAs and their therapeutic and diagnostic significance related to the expression and activity of STAT3 in CRC.
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Affiliation(s)
- Omid Rahbar Farzam
- Department of Medical Biotechnology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Souzan Najafi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Amini
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zohreh Rahimi
- Department of Clinical Biochemistry, Medical School, Daneshgah Avenue, Kermanshah, Iran
- Medical Biology Research Center, Daneshgah Avenue, Kermanshah, Iran
| | - Reza Dabbaghipour
- Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Omid Zohdi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Bahman Akbari
- Department of Medical Biotechnology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Liu S, Li W, Liang L, Zhou Y, Li Y. The regulatory relationship between transcription factor STAT3 and noncoding RNA. Cell Mol Biol Lett 2024; 29:4. [PMID: 38172648 PMCID: PMC10763091 DOI: 10.1186/s11658-023-00521-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 12/12/2023] [Indexed: 01/05/2024] Open
Abstract
Signal transducer and activator of transcription 3 (STAT3), as a key node in numerous carcinogenic signaling pathways, is activated in various tumor tissues and plays important roles in tumor formation, metastasis, and drug resistance. STAT3 is considered a potential subtarget for tumor therapy. Noncoding RNA (ncRNA) is a special type of RNA transcript. Transforming from "junk" transcripts into key molecules involved in cell apoptosis, growth, and functional regulation, ncRNA has been proven to be closely related to various epithelial-mesenchymal transition and drug resistance processes in tumor cells over the past few decades. Research on the relationship between transcription factor STAT3 and ncRNAs has attracted increased attention. To date, existing reviews have mainly focused on the regulation by ncRNAs on the transcription factor STAT3; there has been no review of the regulation by STAT3 on ncRNAs. However, understanding the regulation of ncRNAs by STAT3 and its mechanism is important to comprehensively understand the mutual regulatory relationship between STAT3 and ncRNAs. Therefore, in this review, we summarize the regulation by transcription factor STAT3 on long noncoding RNA, microRNA, and circular RNA and its possible mechanisms. In addition, we provide an update on research progress on the regulation of STAT3 by ncRNAs. This will provide a new perspective to comprehensively understand the regulatory relationship between transcription factor STAT3 and ncRNAs, as well as targeting STAT3 or ncRNAs to treat diseases such as tumors.
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Affiliation(s)
- Siyi Liu
- Department of Nuclear Medicine, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
- Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, 410011, Hunan, China
| | - Wentao Li
- Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, 410011, Hunan, China
| | - Lin Liang
- Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, 410011, Hunan, China
| | - Yanhong Zhou
- Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, 410011, Hunan, China.
| | - Yanling Li
- Department of Nuclear Medicine, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
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Ghasemian A, Omear HA, Mansoori Y, Mansouri P, Deng X, Darbeheshti F, Zarenezhad E, Kohansal M, Pezeshki B, Wang Z, Tang H. Long non-coding RNAs and JAK/STAT signaling pathway regulation in colorectal cancer development. Front Genet 2023; 14:1297093. [PMID: 38094755 PMCID: PMC10716712 DOI: 10.3389/fgene.2023.1297093] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 11/10/2023] [Indexed: 10/17/2024] Open
Abstract
Colorectal cancer (CRC) is one of the main fatal cancers. Cell signaling such as Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling substantially influences the process of gene expression and cell growth. Long non-coding RNAs (lncRNAs) play regulatory roles in cell signaling, cell proliferation, and cancer fate. Hence, lncRNAs can be considered biomarkers in cancers. The inhibitory or activating effects of different lncRNAs on the JAK/STAT pathway regulate cancer cell proliferation or tumor suppression. Additionally, lncRNAs regulate immune responses which play a role in immunotherapy. Mechanisms of lncRNAs in CRC via JAK/STAT regulation mainly include cell proliferation, invasion, metastasis, apoptosis, adhesion, and control of inflammation. More profound findings are warranted to specifically target the lncRNAs in terms of activation or suppression in hindering CRC cell proliferation. Here, to understand the lncRNA cross-talk in CRC through the JAK/STAT signaling pathway, we collected the related in vitro and in vivo data. Future insights may pave the way for the development of novel diagnostic tools, therapeutic interventions, and personalized treatment strategies for CRC patients.
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Affiliation(s)
- Abdolmajid Ghasemian
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Hadeel A. Omear
- College of Science, University of Tikrit University, Tikrit, Iraq
| | - Yaser Mansoori
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Pardis Mansouri
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Xinpei Deng
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China
| | - Farzaneh Darbeheshti
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Elham Zarenezhad
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Maryam Kohansal
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Babak Pezeshki
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
| | - Zhangling Wang
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China
| | - Hailin Tang
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China
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He J, Wu W. Comprehensive landscape and future perspectives of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC): Based on a bibliometric analysis. Noncoding RNA Res 2023; 8:33-52. [PMID: 36311994 PMCID: PMC9582894 DOI: 10.1016/j.ncrna.2022.10.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/03/2022] [Accepted: 10/03/2022] [Indexed: 11/06/2022] Open
Abstract
This review aimed to use bibliometric analysis to sort out, analyze and summarize the knowledge foundation and hot topics in the field of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC), and point out future trends to inspire related research and innovation. We used CiteSpace to analyze publication outputs, countries, institutions, authors, journals, references, and keywords. Knowledge foundations, hotspots, and future trends were then depicted. The overall research showed the trend of biomedical-oriented multidisciplinary. Much evidence indicates that lncRNA plays the role of oncogene or tumor suppressor in the occurrence and development of CRC. Besides, many lncRNAs have multiple mechanisms. lncRNAs and metastasis of CRC, lncRNAs and drug resistance of CRC, and the clinical application of lncRNAs in CRC are current research hotspots. Through insight into the development trend of lncRNAs in CRC, this study will help researchers extract hidden valuable information for further research.
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Affiliation(s)
- Jia He
- Faculty Affairs and Human Resources Management Department, Southwest Medical University, Luzhou, China
| | - Wenhan Wu
- Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, China
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Kang L, Sun J, Liu J, Xu F, Zhu Q, Shi X. Long Non-Coding RNA CASC2 Functions as A Tumor Suppressor in Colorectal Cancer via Modulating The miR-18a-5p/BTG3 Pathway. CELL JOURNAL 2022; 24:665-672. [PMID: 36377216 PMCID: PMC9663961 DOI: 10.22074/cellj.2022.8036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Reportedly, long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is involved in regulating colorectal cancer (CRC) progression. However, the function and detailed downstream mechanism of CASC2 in CRC progression are not fully elucidated. The aim of the study was to investigate the potential function and molecular mechanism of CASC2 in CRC progression. MATERIALS AND METHODS In this experimental study, quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to probe CASC2, microRNA-18a-5p (miR-18a-5p) and B cell translocation gene 3 (BTG3) mRNA expression in CRC tissues and cell lines. After CASC2 was overexpressed in Colo-678 and HCT116 cell lines, methylthiazol tetrazolium (MTT) and 5-bromo-2'-deoxyuridine (BrdU) assays were employed to examine the proliferation of CRC cells. Transwell migration and invasion assays were executed to evaluate the metastatic potential of CRC cells. The targeting relationships among CASC2, miR-18a-5p and BTG3 were validated by dual luciferase reporter gene assay. Western blot assay was applied to examine the regulatory effects of CASC2 and miR-18a-5p on BTG3 protein expression. RESULTS CASC2 was decreased in CRC tissues and cell lines, and its low expression in CRC tissues was associated with larger tumor size and lymph node metastasis. CASC2 overexpression restrained proliferative, migrative and invasive capabilities of CRC cells. CASC2 could function as a molecular sponge for miR-18a-5p and repress the expression of miR-18a-5p. Furthermore, the inhibitory effects of CASC2 on the malignant phenotypes of CRC cells was counteracted by miR-18a-5p mimics. Additionally, CASC2 could positively regulate BTG3 expression via suppressing miR-18a-5p. CONCLUSION CASC2 inhibits CRC development by suppressing miR-18a-5p and raising BTG3 expression.
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Affiliation(s)
- Liumin Kang
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
| | - Jie Sun
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
| | - Jie Liu
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
| | - Feng Xu
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
| | - Qilin Zhu
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
| | - Xiaohua Shi
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
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10
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Ni Y, Low JT, Silke J, O’Reilly LA. Digesting the Role of JAK-STAT and Cytokine Signaling in Oral and Gastric Cancers. Front Immunol 2022; 13:835997. [PMID: 35844493 PMCID: PMC9277720 DOI: 10.3389/fimmu.2022.835997] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 05/16/2022] [Indexed: 12/12/2022] Open
Abstract
When small proteins such as cytokines bind to their associated receptors on the plasma membrane, they can activate multiple internal signaling cascades allowing information from one cell to affect another. Frequently the signaling cascade leads to a change in gene expression that can affect cell functions such as proliferation, differentiation and homeostasis. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) and the tumor necrosis factor receptor (TNFR) are the pivotal mechanisms employed for such communication. When deregulated, the JAK-STAT and the TNF receptor signaling pathways can induce chronic inflammatory phenotypes by promoting more cytokine production. Furthermore, these signaling pathways can promote replication, survival and metastasis of cancer cells. This review will summarize the essentials of the JAK/STAT and TNF signaling pathways and their regulation and the molecular mechanisms that lead to the dysregulation of the JAK-STAT pathway. The consequences of dysregulation, as ascertained from founding work in haematopoietic malignancies to more recent research in solid oral-gastrointestinal cancers, will also be discussed. Finally, this review will highlight the development and future of therapeutic applications which modulate the JAK-STAT or the TNF signaling pathways in cancers.
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Affiliation(s)
- Yanhong Ni
- Central Laboratory, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jun T. Low
- Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia
| | - John Silke
- Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia
| | - Lorraine A. O’Reilly
- Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia
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11
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Akhbari MH, Zafari Z, Sheykhhasan M. Competing Endogenous RNAs (ceRNAs) in Colorectal Cancer: A Review. Expert Rev Mol Med 2022; 24:e27. [PMID: 35748050 DOI: 10.1017/erm.2022.21] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Colorectal cancer (CRC) is a common type of cancer and the second leading cause of cancer-related deaths worldwide. Competing endogenous RNAs (ceRNAs) that contain microRNA response elements (MREs) are involved in CRC progression. They can compete with microRNAs (miRNAs) via their MREs, which can combine non-coding and coding RNAs via complex ceRNA networks. This molecular interaction has the potential to affect a wide variety of biological processes, and many cancers can occur as a result of an imbalanced ceRNA network. Recent research indicates that numerous dysregulated RNAs in CRC may function as ceRNAs, regulating multiple biological functions of the tumour, including proliferation, apoptosis, metastasis, invasion and migration. In this review, we discuss the role of protein-coding and non-coding RNAs, such as long non-coding RNAs, circular RNAs and pseudogenes, in the occurrence of ceRNA networks in CRC, and their function in cancer-related pathways, such as Wnt/β-catenin, mitogen-activated protein kinase and transforming growth factor-β signalling pathways. Additionally, we discuss validated ceRNAs associated with CRC biological functions and their potential role as novel prognostic and diagnostic biomarkers. Examining the role of ceRNAs in CRC sheds new light on cancer treatment and pathogenesis.
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Affiliation(s)
| | - Zahra Zafari
- Department of Biology, Shahed University, Tehran, Iran
| | - Mohsen Sheykhhasan
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture and Research (ACECR), Qom Branch, Qom, Iran
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12
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Potentials of long non-coding RNAs as biomarkers of colorectal cancer. Clin Transl Oncol 2022; 24:1715-1731. [PMID: 35581419 DOI: 10.1007/s12094-022-02834-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 04/04/2022] [Indexed: 02/08/2023]
Abstract
Colorectal cancer (CRC) is the third most common malignant tumor worldwide and the fourth major cause of cancer-related death, with high morbidity and increased mortality year by year. Although significant progress has been made in the therapy strategies for CRC, the great difficulty in early diagnosis, feeble susceptibility to radiotherapy and chemotherapy, and high recurrence rates have reduced therapeutic efficacy resulting in poor prognosis. Therefore, it is urgent to understand the pathogenesis of CRC and unravel novel biomarkers to improve the early diagnosis, treatment and prediction of CRC recurrence. Long non-coding RNAs (lncRNAs) are non-coding RNAs with a length of more than 200 nucleotides, which are abnormally expressed in tumor tissues and cell lines, activating or inhibiting specific genes through multiple mechanisms including transcription and translation. A growing number of studies have shown that lncRNAs are important regulators of microRNAs (miRNAs, miRs) expression in CRC and may be promising biomarkers and potential therapeutic targets in the research field of CRC. This review mainly summarizes the potential application value of lncRNAs as novel biomarkers in CRC diagnosis, radiotherapy, chemotherapy and prognosis. Additionally, the significance of lncRNA SNHGs family and lncRNA-miRNA networks in regulating the occurrence and development of CRC is mentioned, aiming to provide some insights for understanding the pathogenesis of CRC and developing new diagnostic and therapeutic strategies.
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13
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Long Non-Coding RNAs in Pancreatic Cancer: Biologic Functions, Mechanisms, and Clinical Significance. Cancers (Basel) 2022; 14:cancers14092115. [PMID: 35565245 PMCID: PMC9100048 DOI: 10.3390/cancers14092115] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/18/2022] [Accepted: 04/19/2022] [Indexed: 11/17/2022] Open
Abstract
Despite tremendous efforts devoted to research in pancreatic cancer (PC), the mechanism underlying the tumorigenesis and progression of PC is still not completely clear. Additionally, ideal biomarkers and satisfactory therapeutic strategies for clinical application in PC are still lacking. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) might participate in the pathogenesis of diverse cancers, including PC. The abnormal expression of lncRNAs in PC is considered a vital factor during tumorigenesis that affects tumor cell proliferation, migration, invasion, apoptosis, angiogenesis, and drug resistance. With this review of relevant articles published in recent years, we aimed to summarize the biogenesis mechanism, classifications, and modes of action of lncRNAs and to review the functions and mechanisms of lncRNAs in PC. Additionally, the clinical significance of lncRNAs in PC was discussed. Finally, we pointed out the questions remaining from recent studies and anticipated that further investigations would address these gaps in knowledge in this field.
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14
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Song W, Ren J, Xiang R, Yuan W, Fu T. Cross-Talk Between m 6A- and m 5C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients. Front Immunol 2022; 13:740960. [PMID: 35350786 PMCID: PMC8957790 DOI: 10.3389/fimmu.2022.740960] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 02/09/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND N6-methyladenosine (m6A) and 5-methylcytosine (m5C) can modify long non-coding RNAs (lncRNAs), thereby affecting tumorigenesis and tumor progression. However, there is a lack of knowledge regarding the potential roles and cross-talk of m6A- and m5C-related lncRNAs in the tumor microenvironment (TME) and their effect on prognosis. METHODS We systematically evaluated the expression patterns of m6A- and m5C-related lncRNAs in 1358 colorectal cancer (CRC) samples from four datasets. Consensus clustering was conducted to identify molecular subtypes of CRC, and the clinical significance, TME, tumor-infiltrating immune cells (TIICs), and immune checkpoints in the different molecular subtypes were analyzed. Finally, we established a m6A- and m5C-related lncRNA signature and a prognostic nomogram. RESULTS We identified 141 m6A- and m5C-related lncRNAs by co-expression analysis, among which 23 lncRNAs were significantly associated with the overall survival (OS) of CRC patients. Two distinct molecular subtypes (cluster A and cluster B) were identified, and these two distinct molecular subtypes could predict clinicopathological features, prognosis, TME stromal activity, TIICs, immune checkpoints. Next, a m6A- and m5C-related lncRNA signature for predicting OS was constructed, and its predictive capability in CRC patients was validated. We then constructed a highly accurate nomogram for improving the clinical applicability of the signature. Analyses of clinicopathological features, prognosis, TIICs, cancer stem cell (CSC), and drug response revealed significant differences between two risk groups. In addition, we found that patients with a low-risk score exhibited enhanced response to anti-PD-1/L1 immunotherapy. Functional enrichment analysis showed that these lncRNAs related to the high-risk group were involved in the development and progression of CRC. CONCLUSIONS We conducted a comprehensive analysis of m6A- and m5C-related lncRNAs in CRC and revealed their potential functions in predicting tumor-immune-stromal microenvironment, clinicopathological features, and prognosis, and determined their role in immunotherapy. These findings may improve our understanding of the cross-talk between m6A- and m5C-related lncRNAs in CRC and pave a new road for prognosis assessment and more effective immunotherapy strategies.
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Affiliation(s)
| | | | | | | | - Tao Fu
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, China
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15
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Arora S, Khan S, Zaki A, Tabassum G, Mohsin M, Bhutto HN, Ahmad T, Fatma T, Syed MA. Integration of chemokine signaling with non-coding RNAs in tumor microenvironment and heterogeneity in different cancers. Semin Cancer Biol 2022; 86:720-736. [DOI: 10.1016/j.semcancer.2022.03.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 02/15/2022] [Accepted: 03/02/2022] [Indexed: 02/07/2023]
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16
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Olabayo Olatubosun M, Abubakar MB, Batiha GES, Malami I, Ibrahim KG, Abubakar B, Bello MB, Alexiou A, Imam MU. LncRNA SNHG15: A potential therapeutic target in the treatment of colorectal cancer. Chem Biol Drug Des 2022; 101:1138-1150. [PMID: 35191201 DOI: 10.1111/cbdd.14036] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 01/20/2022] [Accepted: 02/14/2022] [Indexed: 11/28/2022]
Abstract
The global burden of colorectal cancer (CRC) is increasing annually. CRC could develop from genetic and phenotypic factors involving changes in gene expression. Incredibly, the human genome transcribes into non-coding RNAs, among which long non-coding RNAs (lncRNAs) signify the most crucial part of the transcriptome in multicellular organisms. lncRNAs affect gene expression at multiple levels, from transcription to protein localization and stability. Recent studies have implicated lncRNA small nucleolar RNA host gene 15 (SNHG15) in cancers occurrence and progression. Previously, an indication suggests SNHG15 overexpression triggers proliferation, metastasis, and impedes apoptosis in CRC. Further, through its activity of binding micro-RNAs, lncRNA SNHG15 modulates genes associated with CRC progression and promotes CRC resistance to chemotherapeutic drugs. Here we reviewed recent findings on the various mechanisms and roles of lncRNA SNHG15 implicated in CRC tumorigenesis. We further highlight how SNHG15 plays a vital role in regulating critical pathways linked to the development and progression of CRC. Finally, we highlight how SNHG15 can be modulated for CRC treatments and the various therapeutic strategies to be implored when targeting SNHG15 in the context of CRC treatments. Findings from these studies present SNHG15 as a potential therapeutic target for preventing and treating CRC.
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Affiliation(s)
- Mutolib Olabayo Olatubosun
- Department of Biochemistry and Molecular Biology, Faculty of Sciences, Usmanu Danfodiyo University, P.M.B 2346, Sokoto, Nigeria.,Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
| | - Murtala Bello Abubakar
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, P.M.B, 2254, Sokoto, Nigeria
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt
| | - Ibrahim Malami
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Pharmacognosy and Ethnopharmacy, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B 2346, Sokoto, Nigeria
| | - Kasimu Ghandi Ibrahim
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, P.M.B, 2254, Sokoto, Nigeria
| | - Bilyaminu Abubakar
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B 2346, Sokoto, Nigeria
| | - Muhammad Bashir Bello
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Veterinary Microbiology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria
| | - Athanasios Alexiou
- Novel Global Community Educational Foundation, Hebersham, Australia.,AFNP Med Austria, Wien, Austria
| | - Mustapha Umar Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, P.M.B. 2346, Sokoto, Nigeria.,Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, P.M.B, 2254, Sokoto, Nigeria
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17
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Jorgensen BG, Ro S. MicroRNAs and 'Sponging' Competitive Endogenous RNAs Dysregulated in Colorectal Cancer: Potential as Noninvasive Biomarkers and Therapeutic Targets. Int J Mol Sci 2022; 23:2166. [PMID: 35216281 PMCID: PMC8876324 DOI: 10.3390/ijms23042166] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 01/28/2022] [Accepted: 02/02/2022] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal (GI) tract in mammals is comprised of dozens of cell types with varied functions, structures, and histological locations that respond in a myriad of ways to epigenetic and genetic factors, environmental cues, diet, and microbiota. The homeostatic functioning of these cells contained within this complex organ system has been shown to be highly regulated by the effect of microRNAs (miRNA). Multiple efforts have uncovered that these miRNAs are often tightly influential in either the suppression or overexpression of inflammatory, apoptotic, and differentiation-related genes and proteins in a variety of cell types in colorectal cancer (CRC). The early detection of CRC and other GI cancers can be difficult, attributable to the invasive nature of prophylactic colonoscopies. Additionally, the levels of miRNAs associated with CRC in biofluids can be contradictory and, therefore, must be considered in the context of other inhibiting competitive endogenous RNAs (ceRNA) such as lncRNAs and circRNAs. There is now a high demand for disease treatments and noninvasive screenings such as testing for bloodborne or fecal miRNAs and their inhibitors/targets. The breadth of this review encompasses current literature on well-established CRC-related miRNAs and the possibilities for their use as biomarkers in the diagnoses of this potentially fatal GI cancer.
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Affiliation(s)
| | - Seungil Ro
- Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA;
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18
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Ji Y, Lv J, Sun D, Huang Y. Therapeutic strategies targeting Wnt/β‑catenin signaling for colorectal cancer (Review). Int J Mol Med 2022; 49:1. [PMID: 34713301 PMCID: PMC8589460 DOI: 10.3892/ijmm.2021.5056] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common carcinomas. Although great progress has been made in recent years, CRC survival remains unsatisfactory due to high metastasis and recurrence. Understanding the underlying molecular mechanisms of CRC tumorigenesis and metastasis has become increasingly important. Recently, aberrant Wnt/β‑catenin signaling has been reported to be strongly associated with CRC tumorigenesis, metastasis and recurrence. Therefore, the Wnt/β‑catenin signaling pathway has potential value as a therapeutic target for CRC. In the present review, the dysregulation of this pathway in CRC and the promoting or suppressing function of therapeutic targets on CRC were explored. In addition, the interaction between this pathway and epithelial‑mesenchymal transition (EMT), cell stemness, mutations, metastasis‑related genes and tumor angiogenesis in CRC cells were also investigated. Numerous studies on this pathway may help identify the potential diagnostic and prognostic markers and therapeutic targets for CRC.
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Affiliation(s)
- Yong Ji
- Department of General Surgery, Jingjiang People's Hospital, Jingjiang, Jiangsu 214500, P.R. China
| | - Jian Lv
- Department of General Surgery, Jingjiang People's Hospital, Jingjiang, Jiangsu 214500, P.R. China
| | - Di Sun
- Department of General Surgery, Jingjiang People's Hospital, Jingjiang, Jiangsu 214500, P.R. China
| | - Yufeng Huang
- Department of Oncology, Jingjiang People's Hospital, Jingjiang, Jiangsu 214500, P.R. China
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19
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Khashkhashi Moghadam S, Bakhshinejad B, Khalafizadeh A, Mahmud Hussen B, Babashah S. Non-coding RNA-associated competitive endogenous RNA regulatory networks: Novel diagnostic and therapeutic opportunities for hepatocellular carcinoma. J Cell Mol Med 2021; 26:287-305. [PMID: 34907642 PMCID: PMC8743668 DOI: 10.1111/jcmm.17126] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 11/09/2021] [Accepted: 12/03/2021] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC), as the most prevalent liver malignancy, is annually diagnosed in more than half a million people worldwide. HCC is strongly associated with hepatitis B and C viral infections as well as alcohol abuse. Obesity and nonalcoholic fatty liver disease (NAFLD) also significantly enhance the risk of liver cancer. Despite recent improvements in therapeutic approaches, patients diagnosed in advanced stages show poor prognosis. Accumulating evidence provides support for the regulatory role of non-coding RNAs (ncRNAs) in cancer. There are a variety of reports indicating the regulatory role of microRNAs (miRNAs) in different stages of HCC. Long non-coding RNAs (LncRNAs) exert their effects by sponging miRNAs and controlling the expression of miRNA-targeted genes. Circular RNAs (circRNAs) perform their biological functions by acting as transcriptional regulators, miRNA sponges and protein templates. Diverse studies have illustrated that dysregulation of competing endogenous RNA networks (ceRNETs) is remarkably correlated with HCC-causing diseases such as chronic viral infections, nonalcoholic steatohepatitis and liver fibrosis/cirrhosis. The aim of the current article was to provide an overview of the role and molecular mechanisms underlying the function of ceRNETs that modulate the characteristics of HCC such as uncontrolled cell proliferation, resistance to cell death, metabolic reprogramming, immune escape, angiogenesis and metastasis. The current knowledge highlights the potential of these regulatory RNA molecules as novel diagnostic biomarkers and therapeutic targets in HCC.
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Affiliation(s)
| | - Babak Bakhshinejad
- Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Khalafizadeh
- Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraq.,Center of Research and Strategic Studies, Lebanese French University, Erbil, Kurdistan Region, Iraq
| | - Sadegh Babashah
- Research and Development Center of Biotechnology, Tarbiat Modares University, Tehran, Iran.,Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
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20
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Matboli M, Shafei AE, Ali MA, El-Din Ahmed TS, Naser M, Abdel-Rahman T, Anber N, Ali M. Role of extracellular LncRNA-SNHG14/miRNA-3940-5p/NAP12 mRNA in colorectal cancer. Arch Physiol Biochem 2021; 127:479-485. [PMID: 31397210 DOI: 10.1080/13813455.2019.1650070] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND We aim to identify and analyze the expression of dyregulated RNAs in colorectal cancer (CRC). METHODS We selected a panel of RNAs specific to CRC composed of Nucleosome Assembly Protein 1 Like 2 (NAP1L2) mRNA, LNCRNA SNHG14 small nucleolar RNA host gene 14 (LNCRNA SNHG14) and homo sapiens microRNA-3940-5p(hsa-miRNA-3940-5p) from genetic and epigenetic databases. Validation of the chosen RNAs was achieved by real time quantitative PCR in sera of patients with CRC, versus controls groups (benign lesions and healthy individual). RESULTS We found that LLNCRNA SNHG14, hsa-miRNA-3940-5p and NAP1L2 mRNA had an excellent performance characteristics and more superior than CEA, and CA19.9 for differentiating CRC from controls. Combined expression of lncRNA SNHG14- hsa-miR-3940-5p and NAP1L2 mRNA had reached 100% sensitivity with accuracy 93%. Interestingly, serum hsa-miRNA-3940-5p could be an independent prognostic factor in CRC. CONCLUSION The extracellular lncRNA SNHG14- hsa-miR-3940-5p - NAP1L2 mRNA may aid in CRC management.KEY MESSAGESThe extracellular RNAs provide a potential class of noninvasive biomarkers with high specificity, accuracy and stability for detection of CRC.We used insilico data analysis followed by qPCR for detection of differential NAP1L2 gene expression with the selected epigenetic regulators.Our data presented interesting biomarker panel (NAP1L2 gene, lncRNA-SNHG14 and hsa-miR-3940-5p) that may be potential for CRC diagnosis and prognosis.
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Affiliation(s)
- Marwa Matboli
- Medical Biochemistry and Molecular Biology Department, Ain Shams Faculty of Medicine, Cairo, Egypt
| | - Ayman E Shafei
- Faculty of Medicine, Modern University for Technology and Information, Cairo, Egypt
| | - Mahmoud A Ali
- Biomedical Research Department, Armed Forces College of Medicine, Cairo, Egypt
| | | | - Mahmoud Naser
- Biomedical Research Department, Armed Forces College of Medicine, Cairo, Egypt
| | - Tamer Abdel-Rahman
- Tropical Medicine Department, Ain Shams Faculty of Medicine, Cairo, Egypt
| | - Nahla Anber
- Fellow of Biochemistry, Mansoura University, Cairo, Egypt
| | - Marwa Ali
- Medical Biochemistry and Molecular Biology Department, Ain Shams Faculty of Medicine, Cairo, Egypt
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21
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Plant isoquinoline alkaloids: Advances in the chemistry and biology of berberine. Eur J Med Chem 2021; 226:113839. [PMID: 34536668 DOI: 10.1016/j.ejmech.2021.113839] [Citation(s) in RCA: 90] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 09/06/2021] [Accepted: 09/07/2021] [Indexed: 01/08/2023]
Abstract
Alkaloids are one of the most important classes of plant bioactives. Among these isoquinoline alkaloids possess varied structures and exhibit numerous biological activities. Basically these are biosynthetically produced via phenylpropanoid pathway. However, occasionally some mixed pathways may also occur to provide structural divergence. Among the various biological activities anticancer, antidiabetic, antiinflammatory, and antimicrobial are important. A few notable bioactive isoquinoline alkaloids are antidiabetic berberine, anti-tussive codeine, analgesic morphine, and muscle relaxant papaverine etc. Berberine is one of the most discussed bioactives from this class possessing broad-spectrum pharmacological activities. Present review aims at recent updates of isoquinoline alkaloids with major emphasis on berberine, its detailed chemistry, important biological activities, structure activity relationship and implementation in future research.
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22
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Xie Q, Zhao S, Kang R, Wang X. lncRNA SNHG11 facilitates prostate cancer progression through the upregulation of IGF‑1R expression and by sponging miR‑184. Int J Mol Med 2021; 48:182. [PMID: 34328198 PMCID: PMC8354307 DOI: 10.3892/ijmm.2021.5015] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 07/07/2021] [Indexed: 11/05/2022] Open
Abstract
Long non‑coding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) has been shown to play an important role in the development and progression of numerous types of cancer. However, to the best of our knowledge, the role of SNHG11 in prostate cancer (PCa) development and metastasis remains unclear. Thus, the aim of the present study was to investigate the functional role and molecular mechanisms of SNHG11 in PCa progression. It was revealed that the SNHG11 expression levels were significantly upregulated in PCa tissues, in comparison with those in adjacent normal tissues. Functionally, SNHG11 knockdown significantly suppressed PCa cell proliferation, migration, invasion and metastasis in vitro and in vivo. Furthermore, SNHG11 was found to positively regulate insulin‑like growth factor 1 receptor (IGF‑1R) expression by sponging microRNA (miRNA/miR)‑184 in PCa cells. The results of rescue experiments demonstrated that IGF‑1R overexpression reversed the suppressive effects of SNHG11 knockdown on the proliferation, migration and invasion of PCa cells. On the whole, the findings of the present study suggest that SNHG11 expression is upregulated in PCa and that it facilitates PCa progression, at least in part, via the modulation of the miR‑184/IGF‑1R signaling axis.
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Affiliation(s)
- Qiang Xie
- Department of Reproduction, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong 523059, P.R. China
| | - Shankun Zhao
- Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Zhejiang, Taizhou 318000, P.R. China
| | - Ran Kang
- Department of Urology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
| | - Xiaolan Wang
- Reproductive Center of Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
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23
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Zhang P, Pan Y, Sun J, Pan G. Aberrant expression of LncRNA CASC2 mediated the cell viability, apoptosis and autophagy of colon cancer cells by sponging miR-19a via NF-κB signaling pathway. Int J Exp Pathol 2021; 102:163-171. [PMID: 33983643 PMCID: PMC8139380 DOI: 10.1111/iep.12393] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 01/17/2021] [Accepted: 02/11/2021] [Indexed: 12/14/2022] Open
Abstract
Abnormal and rapid proliferation of colon cancer cells is a severe problem that can be regulated by non-coding RNAs. Thus, our study focused on effects of lncRNA CASC2 and miR-19a on colon cancer cells. Expressions of lncRNA CASC2, miR-19a, Bcl-2, Bax and NF-κB/p65 were examined by RT-qPCR. Cell viabilities were detected by CCK-8. A luciferase report assay was used for measuring binding conditions between lncRNA CASC2 and miR-19a. Western blotting was used to evaluate expression of LC3-I, LC3-II and p62 related to autophagy. Expression of lncRNA CASC2 lower in cancer cell lines and the overexpression reduced the cell viability of HT29 and SW480. Furthermore, Bcl-2 was suppressed by overexpressed lncRNA CASC2, while Bax was upregulated. LC3-Ⅰ and p62 were both inhibited, but LC3-Ⅱ was promoted. MiR-19a was predicted to bind lncRNA CASC2 and expressed higher in cancer cell lines. Overexpressed miR-19a reduced expression of lncRNA CASC2 and increased cell viability. This was repressed by upregulated lncRNA CASC2. Bcl-2 and Bax expression and proteins implicated in autophagy that are regulated by lncRNA CASC2 upregulation were reversed by miR-19a overexpression. NF-κB was upregulated in colon cancer cell lines, while inhibition of NF-κB reversed functions of lncRNA CASC2 and magnified roles of miR-19a. Our findings showed that lncRNA CASC2 inhibited cell viability in colon cancer cell lines and miR-19a reversed its functions through the NF-κB signalling pathway, suggesting that these could be factors in treating colon cancer in the future.
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Affiliation(s)
- Peng Zhang
- Affiliated Hospital of Shaanxi University of Chinese MedicineXian CityChina
| | - Yan Pan
- Affiliated Hospital of Shaanxi University of Chinese MedicineXian CityChina
| | - Jujun Sun
- Affiliated Hospital of Shaanxi University of Chinese MedicineXian CityChina
| | - Gaiyan Pan
- Affiliated Hospital of Shaanxi University of Chinese MedicineXian CityChina
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24
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Yang Y, Yan X, Li X, Ma Y, Goel A. Long non-coding RNAs in colorectal cancer: Novel oncogenic mechanisms and promising clinical applications. Cancer Lett 2021; 504:67-80. [PMID: 33577977 PMCID: PMC9715275 DOI: 10.1016/j.canlet.2021.01.009] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 12/29/2020] [Accepted: 01/08/2021] [Indexed: 02/05/2023]
Abstract
Colorectal cancer (CRC) is the third most common malignancy and ranks as the second leading cause of cancer-related deaths worldwide. Despite the improvements in CRC diagnosis and treatment approaches, a considerable proportion of CRC patients still suffers from poor prognosis due to late disease detections and lack of personalized disease managements. Recent evidences have not only provided important molecular insights into their mechanistic behaviors but also indicated that identification of cancer-specific long non-coding RNAs (LncRNAs) could benefit earlier disease detections and improve treatment outcomes in patients suffering from CRC. LncRNAs have raised extensive attentions as they participate in various hallmarks of CRC. The mechanistic evidence gleaned in the recent decade clearly reveals that lncRNAs exert their oncogenic roles by regulating autophagy, epigenetic modifications, enhancing stem phenotype and modifying tumor microenvironment. In view of their pleiotropic functional roles in malignant progression, and their frequently dysregulated expression in CRC patients, they have great potential to be reliable diagnostic and prognostic biomarkers, as well as therapeutic targets for CRC. In the present review, we will focus on the oncogenic roles of lncRNAs and related mechanisms in CRC as well as discuss their clinical potential in the early diagnosis, prognostic prediction and therapeutic translation in patients with this malignancy.
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Affiliation(s)
- Yufei Yang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xuebing Yan
- Department of Oncology, Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Xinxiang Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Yanlei Ma
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
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25
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lncRNA SNHG4 modulates colorectal cancer cell cycle and cell proliferation through regulating miR-590-3p/CDK1 axis. Aging (Albany NY) 2021; 13:9838-9858. [PMID: 33744866 PMCID: PMC8064176 DOI: 10.18632/aging.202737] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 02/08/2021] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is a prevalent malignancy worldwide. The development of genome sequencing technology has allowed the discovery that epigenetic regulation might play a critical role in CRC tumorigenesis. In the present study, we found that the long noncoding RNA (lncRNA) SNHG4 was dramatically increased in CRC tissue samples and cell lines based on both publicly available and experimental data. SNHG4 knockdown suppressed the viability and colony formation capacity of CRC cells. The expression of CDK1 was considerably increased in CRC tissue samples and cells and had a positive correlation with the expression of SNHG4 in CRC. SNHG4 silencing not only caused S phase cell cycle arrest but also significantly downregulated the CDK1, cyclin B1, and cyclin A2 protein levels in CRC cells. miR-590-3p simultaneously bound to SNHG4 and CDK1. miR-590-3p functioned to inhibit CDK1 expression. miR-590-3p overexpression exerted the same effects on the CRC cell phenotype as SNHG4 knockdown. The effects of si-SNHG4 on CRC cells were significantly reversed by anti-miR-590-3p, indicating that SNHG4 relieved the miR-590-3p-induced inhibition of CDK1 by acting as a competing endogenous RNA (ceRNA). In vivo, SNHG4 silencing inhibited subcutaneously transplanted tumor growth and decreased cell cycle marker levels, whereas miR-590-3p inhibition exerted the opposite effects. The in vivo effects of SNHG4 silencing were also reversed by miR-590-3p inhibition. The SNHG4/miR-590-3p/CDK1 axis influences the cell cycle to modulate CRC cell proliferation and subcutaneously transplanted tumor growth. Further application of this axis still requires analysis using more animal models and clinical investigations.
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Kalhori MR, Khodayari H, Khodayari S, Vesovic M, Jackson G, Farzaei MH, Bishayee A. Regulation of Long Non-Coding RNAs by Plant Secondary Metabolites: A Novel Anticancer Therapeutic Approach. Cancers (Basel) 2021; 13:cancers13061274. [PMID: 33805687 PMCID: PMC8001769 DOI: 10.3390/cancers13061274] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 03/05/2021] [Accepted: 03/09/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Cancer is caused by the rapid and uncontrolled growth of cells that eventually lead to tumor formation. Genetic and epigenetic alterations are among the most critical factors in the onset of carcinoma. Phytochemicals are a group of natural compounds that play an essential role in cancer prevention and treatment. Long non-coding RNAs (lncRNAs) are potential therapeutic targets of bioactive phytochemicals, and these compounds could regulate the expression of lncRNAs directly and indirectly. Here, we critically evaluate in vitro and in vivo anticancer effects of phytochemicals in numerous human cancers via regulation of lncRNA expression and their downstream target genes. Abstract Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs that play an essential role in various cellular activities, such as differentiation, proliferation, and apoptosis. Dysregulation of lncRNAs serves a fundamental role in the progression and initiation of various diseases, including cancer. Precision medicine is a suitable and optimal treatment method for cancer so that based on each patient’s genetic content, a specific treatment or drug is prescribed. The rapid advancement of science and technology in recent years has led to many successes in this particular treatment. Phytochemicals are a group of natural compounds extracted from fruits, vegetables, and plants. Through the downregulation of oncogenic lncRNAs or upregulation of tumor suppressor lncRNAs, these bioactive compounds can inhibit metastasis, proliferation, invasion, migration, and cancer cells. These natural products can be a novel and alternative strategy for cancer treatment and improve tumor cells’ sensitivity to standard adjuvant therapies. This review will discuss the antineoplastic effects of bioactive plant secondary metabolites (phytochemicals) via regulation of expression of lncRNAs in various human cancers and their potential for the treatment and prevention of human cancers.
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Affiliation(s)
- Mohammad Reza Kalhori
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran;
| | - Hamid Khodayari
- International Center for Personalized Medicine, 40235 Düsseldorf, Germany; (H.K.); (S.K.)
- Breast Disease Research Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran
| | - Saeed Khodayari
- International Center for Personalized Medicine, 40235 Düsseldorf, Germany; (H.K.); (S.K.)
- Breast Disease Research Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran
| | - Miko Vesovic
- Department of Mathematics, Statistics, and Computer Science, University of Illinois at Chicago, Chicago, IL 60607, USA;
| | - Gloria Jackson
- Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA;
| | - Mohammad Hosein Farzaei
- Medical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6718874414, Iran
- Correspondence: (M.H.F.); or (A.B.)
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA;
- Correspondence: (M.H.F.); or (A.B.)
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27
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Chen J, Liu Y, Min J, Wang H, Li F, Xu C, Gong A, Xu M. Alternative splicing of lncRNAs in human diseases. Am J Cancer Res 2021; 11:624-639. [PMID: 33791145 PMCID: PMC7994174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 12/17/2020] [Indexed: 06/12/2023] Open
Abstract
Alternative splicing (AS), a vital post-transcription process for eukaryote gene expression regulating, can efficiently improve gene utilization and increase the variety of RNA transcripts and proteins. However, AS of non-coding RNAs (ncRNAs) has not been paid enough attention to compared with that of protein-coding RNAs (mRNAs) for a long time. In fact, AS of ncRNAs, especially long noncoding RNAs (lncRNAs), also plays a significant regulatory role in the human disease. Recently, some bifunctional genes transcribed into both mRNA and lncRNA transcripts by AS have been observed. Here, we focus on the AS of lncRNAs and bifunctional genes producing lncRNA transcripts and propose a strategy for the future research of lncRNA AS.
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Affiliation(s)
- Jiaxi Chen
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu UniversityZhenjiang 212001, Jiangsu, China
| | - Yawen Liu
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu UniversityZhenjiang 212001, Jiangsu, China
| | - Jingyu Min
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu UniversityZhenjiang 212001, Jiangsu, China
| | - Huizhi Wang
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu UniversityZhenjiang 212001, Jiangsu, China
| | - Feifan Li
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu UniversityZhenjiang 212001, Jiangsu, China
| | - Chunhui Xu
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu UniversityZhenjiang 212001, Jiangsu, China
| | - Aihua Gong
- Department of Cell Biology, School of Medicine, Jiangsu UniversityZhenjiang 212013, Jiangsu, China
| | - Min Xu
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu UniversityZhenjiang 212001, Jiangsu, China
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28
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Zhao H, De Souza C, Kumar VE, Nambiar R, Hao D, Zhu X, Luo Y, Liu S, Zhang L, Zhu J. Long non-coding RNA signatures as predictors of prognosis in thyroid cancer: a narrative review. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:359. [PMID: 33708986 PMCID: PMC7944284 DOI: 10.21037/atm-20-8191] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 01/26/2021] [Indexed: 02/05/2023]
Abstract
Thyroid cancer (TC) is the most common endocrine malignancy, with high incidence rates in recent decades. Most TC cases have good prognoses, but a high risk of recurrence and metastases poses challenges, especially for patients with high-risk factors. Currently used prognostic markers for TC involve a combination of genetic factors and overexpressed proteins. Long non-coding RNAs (lncRNAs) regulate several integral biologic processes by playing key roles in the transcription of several downstream targets maintaining cellular behavior. Prior studies have revealed that lncRNAs promote tumor cell proliferation, invasion, metastasis, and angiogenesis, making them important targets for therapeutic intervention in cancer. While the exact molecular mechanisms underlying the role of lncRNAs in modulating TC progression and recurrence is still unclear, it is important to note that some lncRNAs are upregulated in certain cancers, while others are downregulated. In the present study, we review several key lncRNAs, their association with cancer progression, and the important roles they may play as tumor suppressors or tumor promoters in tumorigenesis. We discuss the potential mechanisms of lncRNA-mediated pathogenesis that can be targeted for the treatment of TC, the existing and potential benefits of using lncRNAs as diagnostic and prognostic measures for cancer detection, and tumor burden in patients.
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Affiliation(s)
- Hongyuan Zhao
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Cristabelle De Souza
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Sacramento, CA, USA
- Institute for Regenerative Medicine and Stem Cell Research, Stanford University, Stanford, CA, USA
| | - Vigneshwari Easwar Kumar
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Sacramento, CA, USA
| | - Roshni Nambiar
- Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Sacramento, CA, USA
| | - Dake Hao
- Department of Surgery, School of Medicine, University of California, Sacramento, CA, USA
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA, USA
| | - Xiaofeng Zhu
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yi Luo
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Shengshan Liu
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Lingyun Zhang
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jingqiang Zhu
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, China
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29
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Zhang Y, Zhou H, Zhang M, Xing L, Yang C, Xia B, Lou G. Integrated analysis of a competing endogenous RNA network reveals an 11-lncRNA prognostic signature in ovarian cancer. Aging (Albany NY) 2020; 12:25153-25171. [PMID: 33223503 PMCID: PMC7803494 DOI: 10.18632/aging.104116] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 09/09/2020] [Indexed: 01/22/2023]
Abstract
Long noncoding RNA (lncRNA) can function as a competing endogenous RNA (ceRNA) involved in tumor initiation and progression. However, the prognostic roles of lncRNAs in the integrated analysis of the ceRNA network in ovarian cancer (OVC) are still lacking. This study aimed to identify lncRNAs associated with the prognosis of OVC. Differential expression analysis and WGCNA were used to screen OVC-specific RNAs. A lncRNA-miRNA-mRNA regulatory network consisting of 201 lncRNAs, 85 miRNA and 146 mRNAs was constructed, and functional enrichment and protein-protein network analyses were performed. Then, the OVC-specific RNAs were submitted to Cox regression analysis. Twelve differentially expressed lncRNAs and mRNAs were identified as significantly associated with OS of OVC patients. Meanwhile, 11 lncRNAs (including C4A-AS1, LINC02408, LINC00488) were established as prognostic risk formulas. The low-risk group had better OS and DFS than the high-risk group (P <0.01). Univariate and multivariate Cox regression analyses revealed the 11-lncRNA risk score as an independent prognostic factor. A prognostic nomogram was developed based on independent prognostic factors. Our data provide evidence that the 11-lncRNA signature could serve as an independent prognostic indicator. This study also suggests that these 11 lncRNAs potentially participate in the progression of OVC.
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Affiliation(s)
- Yongjian Zhang
- Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Hu Zhou
- Department of Gynecology Oncology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Meiyin Zhang
- Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Linan Xing
- Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Chang Yang
- Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Bairong Xia
- Department of Gynecology Oncology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Ge Lou
- Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
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Skiriute D, Stakaitis R, Steponaitis G, Tamasauskas A, Vaitkiene P. The Role of CASC2 and miR-21 Interplay in Glioma Malignancy and Patient Outcome. Int J Mol Sci 2020; 21:E7962. [PMID: 33120918 PMCID: PMC7663706 DOI: 10.3390/ijms21217962] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 10/19/2020] [Accepted: 10/21/2020] [Indexed: 12/21/2022] Open
Abstract
Recently long non-coding RNAs (lncRNAs) were highlighted for their regulatory role in tumor biology. The novel human lncRNA cancer susceptibility candidate 2 (CASC2) has been characterized as a potential tumor suppressor in several tumor types. However, the roles of CASC2 and its interplay with miR-21 in different malignancy grade patient gliomas remain unexplored. Here we screened 99 different malignancy grade astrocytomas for CASC2, and miR-21 gene expression by real-time quantitative polymerase chain reaction (RT-qPCR) in isocitrate dehydrogenase 1 (IDH1) and O-6-methylguanine methyltransferase (MGMT) assessed gliomas. CASC2 expression was significantly downregulated in glioblastomas (p = 0.0003). Gliomas with low CASC2 expression exhibited a high level of miR-21, which was highly associated with the higher glioma grade (p = 0.0001), IDH1 wild type gliomas (p < 0.0001), and poor patient survival (p < 0.001). Taken together, these observations suggest that CASC2 acts as a tumor suppressor and potentially as a competing endogenous RNA (ceRNA) for miR-21, plays important role in IDH1 wild type glioma pathogenesis and patients' outcomes.
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Affiliation(s)
- Daina Skiriute
- Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania; (R.S.); (G.S.); (A.T.)
| | - Rytis Stakaitis
- Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania; (R.S.); (G.S.); (A.T.)
| | - Giedrius Steponaitis
- Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania; (R.S.); (G.S.); (A.T.)
| | - Arimantas Tamasauskas
- Laboratory of Molecular Neurooncology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania; (R.S.); (G.S.); (A.T.)
| | - Paulina Vaitkiene
- Laboratory of Molecular Neurobiology, Neuroscience Institute, Lithuanian University of Health Sciences, Eiveniu str. 4, LT-50161 Kaunas, Lithuania;
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31
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Long non-coding RNA CASC2 targeting miR-18a suppresses glioblastoma cell growth, metastasis and EMT in vitro and in vivo. J Biosci 2020. [PMID: 32975234 DOI: 10.1007/s12038-020-00077-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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32
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Mei H, Wen Y. MicroRNAs for Diagnosis and Treatment of Colorectal Cancer. Endocr Metab Immune Disord Drug Targets 2020; 21:47-55. [PMID: 32819240 DOI: 10.2174/1871530320999200818134339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 05/28/2020] [Accepted: 07/15/2020] [Indexed: 11/22/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, with high morbidity and mortality rates. The diagnosis and treatment of CRC have the most significant value for disease- free survival. Early diagnosis and early surgical resection are generally considered to be the most effective ways to reduce CRC mortality. In the past few years, many researchers have focused on the role of microRNAs in different tumors, making the functions of microRNAs gradually clear. The present study reviews the role of microRNAs in the diagnosis and treatment of colorectal cancer. Compared with the usual diagnosis methods and biomarker, circulating microRNAs can be promising new effective biomarkers for CRC diagnosis and treatment.
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Affiliation(s)
- Haitao Mei
- Shanghai General Hospital, Department of general surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yugang Wen
- Shanghai General Hospital, Department of general surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Kolenda T, Guglas K, Kopczyńska M, Sobocińska J, Teresiak A, Bliźniak R, Lamperska K. Good or not good: Role of miR-18a in cancer biology. Rep Pract Oncol Radiother 2020; 25:808-819. [PMID: 32884453 DOI: 10.1016/j.rpor.2020.07.006] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 04/24/2020] [Accepted: 07/31/2020] [Indexed: 02/06/2023] Open
Abstract
miR-18a is a member of primary transcript called miR-17-92a (C13orf25 or MIR17HG) which also contains five other miRNAs: miR-17, miR-19a, miR-20a, miR-19b and miR-92a. This cluster as a whole shows specific characteristics, where miR-18a seems to be unique. In contrast to the other members, the expression of miR-18a is additionally controlled and probably functions as its own internal controller of the cluster. miR-18a regulates many genes involved in proliferation, cell cycle, apoptosis, response to different kinds of stress, autophagy and differentiation. The disturbances of miR-18a expression are observed in cancer as well as in different diseases or pathological states. The miR-17-92a cluster is commonly described as oncogenic and it is known as 'oncomiR-1', but this statement is a simplification because miR-18a can act both as an oncogene and a suppressor. In this review we summarize the current knowledge about miR-18a focusing on its regulation, role in cancer biology and utility as a potential biomarker.
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Key Words
- 5-FU, 5-fluorouracyl
- ACVR2A, activin A receptor type 2A
- AKT, AKT serine/threonine kinase
- AR, androgen receptor
- ATG7, autophagy related 7
- ATM, ATM serine/threonine kinase
- BAX, BCL2 associated Xapoptosis regulator
- BCL2, BCL2 apoptosis regulator
- BCL2L10, BCL2 like 10
- BDNF, brain derived neurotrophic factor
- BLCA, bladder urothelial carcinoma
- BRCA, breast cancer
- Biomarker
- Bp, base pair
- C-myc (MYCBP), MYC binding protein
- CASC2, cancer susceptibility 2
- CD133 (PROM1), prominin 1
- CDC42, cell division cycle 42
- CDKN1, Bcyclin dependent kinase inhibitor 1B
- COAD, colon adenocarcinoma
- Cancer
- Circulating miRNA
- DDR, DNA damage repair
- E2F family (E2F1, E2F2, E2F3), E2F transcription factors
- EBV, Epstein-Barr virus
- EMT, epithelial-to-mesenchymal transition
- ER, estrogen receptor
- ERBB (EGFR), epidermal growth factor receptor
- ESCA, esophageal carcinoma
- FENDRR, FOXF1 adjacent non-coding developmental regulatory RNA
- FER1L4, fer-1 like family member 4 (pseudogene)
- GAS5, growth arrest–specific 5
- HIF-1α (HIF1A), hypoxia inducible factor 1 subunit alpha
- HNRNPA1, heterogeneous nuclear ribonucleoprotein A1
- HNSC, head and neck squamous cell carcinoma
- HRR, homologous recombination-based DNA repair
- IFN-γ (IFNG), interferon gamma
- IGF1, insulin like growth factor 1
- IL6, interleukin 6
- IPMK, inositol phosphate multikinase
- KIRC, clear cell kidney carcinoma
- KIRP, kidney renal papillary cell carcinoma
- KRAS, KRAS proto-oncogene, GTPase
- LIHC, liver hepatocellular carcinoma
- LMP1, latent membrane protein 1
- LUAD, lung adenocarcinoma
- LUSC, lung squamous cell carcinoma
- Liquid biopsy
- MAPK, mitogen-activated protein kinase
- MCM7, minichromosome maintenance complex component 7
- MET, mesenchymal-to-epithelial transition
- MTOR, mechanistic target of rapamycin kinase
- N-myc (MYCN), MYCN proto-oncogene, bHLH transcription factor
- NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells
- NOTCH2, notch receptor 2
- Oncogene
- PAAD, pancreatic adenocarcinoma
- PERK (EIF2AK3), eukaryotic translation initiation factor 2 alpha kinase 3
- PI3K (PIK3CA), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
- PIAS3, protein inhibitor of activated STAT 3
- PRAD, prostate adenocarcinoma
- RISC, RNA-induced silencing complex
- SMAD2, SMAD family member 2
- SMG1, SMG1 nonsense mediated mRNA decay associated PI3K related kinase
- SNHG1, small nucleolar RNA host gene 1
- SOCS5, suppressor of cytokine signaling 5
- STAD, stomach adenocarcinoma
- STAT3, signal transducer and activator of transcription 3
- STK4, serine/threonine kinase 4
- Suppressor
- TCGA
- TCGA, The Cancer Genome Atlas
- TGF-β (TGFB1), transforming growth factor beta 1
- TGFBR2, transforming growth factor beta receptor 2
- THCA, papillary thyroid carcinoma
- TNM, Classification of Malignant Tumors: T - tumor / N - lymph nodes / M – metastasis
- TP53, tumor protein p53
- TP53TG1, TP53 target 1
- TRIAP1, p53-regulating inhibitor of apoptosis gene
- TSC1, TSC complex subunit 1
- UCA1, urothelial cancer associated 1
- UCEC, uterine corpus endometrial carcinoma
- UTR, untranslated region
- WDFY3-AS2, WDFY3 antisense RNA 2
- WEE1, WEE1 G2 checkpoint kinase
- WNT family, Wingless-type MMTV integration site family/Wnt family ligands
- ZEB1/ZEB2, zinc finger E-box binding homeobox 1 and 2
- ceRNA, competitive endogenous RNA
- cncRNA, protein coding and non-coding RNA
- lncRNA, long-non coding RNA
- miR-17-92a
- miR-18a
- miRNA
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Affiliation(s)
- Tomasz Kolenda
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland.,Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland.,Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warszawa, Poland
| | - Kacper Guglas
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland.,Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warszawa, Poland
| | - Magda Kopczyńska
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland.,Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland
| | - Joanna Sobocińska
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland
| | - Anna Teresiak
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
| | - Renata Bliźniak
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
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Zeng J, Chen JY, Meng J, Chen Z. Inflammation and DNA methylation coregulate the CtBP-PCAF-c-MYC transcriptional complex to activate the expression of a long non-coding RNA CASC2 in acute pancreatitis. Int J Biol Sci 2020; 16:2116-2130. [PMID: 32549759 PMCID: PMC7294942 DOI: 10.7150/ijbs.43557] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 04/20/2020] [Indexed: 02/06/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are emerging as important regulators involved in the pathogenesis of many diseases. However, it is still unknown if they contribute to the occurrence of acute pancreatitis (AP). Here, we identified a lncRNA CASC2 (Cancer Susceptibility Candidate 2) was significantly upregulated in the pancreatic tissues from AP patients. Knockdown or overexpression of CASC2 in vitro could specifically repress or induce the expression of two proinflammatory cytokines including IL6 (Interleukin 6) and IL17, respectively. Changing the expression levels of several transcription factors that were predicted to bind to the promoter of CASC2, we found c-MYC could specifically regulate the expression of CASC2. Using immunoprecipitation, mass spectrometry, and co-immunoprecipitation assays, we proved that c-MYC assembled a transcriptional complex with PCAF (p300/CBP-associated Factor) and CtBP1/2 (C-terminal Binding Protein 1 and 2), terming as the CtBP-PCAF-c-MYC (CPM) complex. Further investigation revealed that CtBPs were amplified in the pancreatic tissues from AP patients and they functioned as coactivators to induce the expression of CASC2 and thus led to the upregulation of IL6 and IL17. Moreover, we identified that decreased DNA methylation levels in the promoters of CtBPs and inflammatory stimuli coactivated the expression of CtBPs. Collectively, we identified a new signaling pathway in which DNA methylation and inflammatory stimuli coregulate the CPM complex to activate CASC2 expression, whose induction further activates the expression of IL6 and IL17, eventually aggravating inflammation response and causing the pathology of AP.
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Affiliation(s)
- Jun Zeng
- Department of Gastroenterology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China
| | - Jian-Yong Chen
- Department of Gastroenterology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China
| | - Jun Meng
- Department of Gastroenterology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China
| | - Zhi Chen
- Department of critical care medicine, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China.,Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
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Targeting of oncogenic signaling pathways by berberine for treatment of colorectal cancer. Med Oncol 2020; 37:49. [PMID: 32303850 DOI: 10.1007/s12032-020-01367-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 03/18/2020] [Indexed: 12/12/2022]
Abstract
Studies indicate that inhibiting a single signaling pathway or one single product of a gene is insufficient for the prevention and treatment of cancer. This is due to the fact that dysregulation must occur in more than 500 genes in order to produce a cancerous phenotype. Despite this evidence, available drugs used for cancer treatment focus on a single target. Meanwhile, berberine as a nutraceutical is capable of targeting various processes involved in tumor development including proliferation, invasion, angiogenesis, and metastasis. In comparison with synthetic agents, berberine is cheaper, safer, and more available. Berberine has shown anti-inflammatory properties which make it an ideal option in order to prevent inflammation-associated cancers. Colorectal cancer is one of the most common cancers all over the world and its incidence is increasing each day. Therefore, further investigations about berberine could be helpful in the discovery of novel agents for preventing and/or treating colorectal cancer. This review emphasizes the studies investigating the roles of berberine in colorectal cancer such as controlling cell signaling pathways, inducing apoptosis, regulating microRNAs, attenuating oxidative stress, and affecting inflammation.
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Fattahi S, Kosari-Monfared M, Golpour M, Emami Z, Ghasemiyan M, Nouri M, Akhavan-Niaki H. LncRNAs as potential diagnostic and prognostic biomarkers in gastric cancer: A novel approach to personalized medicine. J Cell Physiol 2020; 235:3189-3206. [PMID: 31595495 DOI: 10.1002/jcp.29260] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 09/03/2019] [Indexed: 02/06/2023]
Abstract
Gastric cancer is the third leading cause of cancer death with 5-year survival rate of about 30-35%. Since early detection is associated with decreased mortality, identification of novel biomarkers for early diagnosis and proper management of patients with the best response to therapy is urgently needed. Long noncoding RNAs (lncRNAs) due to their high specificity, easy accessibility in a noninvasive manner, as well as their aberrant expression under different pathological and physiological conditions, have received a great attention as potential diagnostic, prognostic, or predictive biomarkers. They may also serve as targets for treating gastric cancer. In this review, we highlighted the role of lncRNAs as tumor suppressors or oncogenes that make them potential biomarkers for the diagnosis and prognosis of gastric cancer. Relatively, lncRNAs such as H19, HOTAIR, UCA1, PVT1, tissue differentiation-inducing nonprotein coding, and LINC00152 could be potential diagnostic and prognostic markers in patients with gastric cancer. Also, the impact of lncRNAs such as ecCEBPA, MLK7-AS1, TUG1, HOXA11-AS, GAPLINC, LEIGC, multidrug resistance-related and upregulated lncRNA, PVT1 on gastric cancer epigenetic and drug resistance as well as their potential as therapeutic targets for personalized medicine was discussed.
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Affiliation(s)
- Sadegh Fattahi
- Department of Genetics, Student Research Committee, Babol University of Medical Sciences, Babol, Iran
- Department of Genetics, Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
- Department of Biochemistry, North Research Center, Pasteur Institute, Amol, Iran
| | | | - Monireh Golpour
- Department of Immunology, Molecular and Cell Biology Research Center, Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Zakieh Emami
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mohammad Ghasemiyan
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Nouri
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Haleh Akhavan-Niaki
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
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Kazimierczyk M, Kasprowicz MK, Kasprzyk ME, Wrzesinski J. Human Long Noncoding RNA Interactome: Detection, Characterization and Function. Int J Mol Sci 2020; 21:E1027. [PMID: 32033158 PMCID: PMC7037361 DOI: 10.3390/ijms21031027] [Citation(s) in RCA: 131] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 01/31/2020] [Accepted: 02/02/2020] [Indexed: 01/17/2023] Open
Abstract
The application of a new generation of sequencing techniques has revealed that most of the genome has already been transcribed. However, only a small part of the genome codes proteins. The rest of the genome "dark matter" belongs to divergent groups of non-coding RNA (ncRNA), that is not translated into proteins. There are two groups of ncRNAs, which include small and long non-coding RNAs (sncRNA and lncRNA respectively). Over the last decade, there has been an increased interest in lncRNAs and their interaction with cellular components. In this review, we presented the newest information about the human lncRNA interactome. The term lncRNA interactome refers to cellular biomolecules, such as nucleic acids, proteins, and peptides that interact with lncRNA. The lncRNA interactome was characterized in the last decade, however, understanding what role the biomolecules associated with lncRNA play and the nature of these interactions will allow us to better understand lncRNA's biological functions in the cell. We also describe a set of methods currently used for the detection of lncRNA interactome components and the analysis of their interactions. We think that such a holistic and integrated analysis of the lncRNA interactome will help to better understand its potential role in the development of organisms and cancers.
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Affiliation(s)
| | | | | | - Jan Wrzesinski
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland (M.K.K.); (M.E.K.)
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Tiansheng G, Junming H, Xiaoyun W, Peixi C, Shaoshan D, Qianping C. lncRNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promotes Proliferation and Invasion of Non-Small Cell Lung Cancer Cells via Down-Regulating miR-202 Expression. CELL JOURNAL 2019; 22:375-385. [PMID: 31863664 PMCID: PMC6947012 DOI: 10.22074/cellj.2020.6837] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 02/06/2019] [Indexed: 12/27/2022]
Abstract
Objective Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play key roles in cancer. This study
aims to clarify role of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in non-small cell lung
cancer (NSCLC) and uncover the underlying mechanisms.
Materials and Methods In this experimental study, MALAT1 and miR-202 expression in tissues and cell lines were
detected using quantitative real time polymerase chain reaction (qRT-PCR) assay. Cell transfection was conducted
using Lipofectamine 3000. Cell proliferation was determined with CCK-8 assay. MMP2 and MMP9 expressions were
measured with Western blot. Cell invasive ability was evaluated by Transwell assay. Starbase 2.0 tool was used to
predict targets of MALAT1. Dual luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA
pull-down assay were conducted to confirm the potential direct interaction between MALAT1 and miR-202.
Results MALAT1 was overexpressed in NSCLC samples and cell lines. High expression of MALAT1 was related
to large tumor size (>3 cm), poor histological grade, advanced cancer and tumor metastasis in NSCLC. In vitro
assays exhibited that knockdown of MALAT1 remarkably decreased A549 cell growth and invasion capacity, while
overexpression of MALAT1 significantly enhanced NCI-H292 cell proliferation and invasion ability. Next, we verified that
MALAT1 could act as a competing endogenous RNA (ceRNA) by sponging miR-202 in NSCLC and there is a negative
correlation between MALAT1 and miR-202. Besides, overexpression of miR-202 inhibited cell proliferation and invasive
ability in MALAT1-overexpressed cells.
Conclusion This study demonstrated that lncRNA-MALAT1 gets involved in NSCLC progression by targeting miR-
202, indicating that MALAT1 may serve as a novel therapeutic target for NSCLC treatment.
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Affiliation(s)
- Guo Tiansheng
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China. Electronic Address:
| | - Huang Junming
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China. Electronic Address:
| | - Wan Xiaoyun
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China. Electronic Address:
| | - Chen Peixi
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China
| | - Du Shaoshan
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China
| | - Chen Qianping
- Department of Oncology, Guangzhou Panyu Hospital of Chinese Medicine, Guangzhou, PR China
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Owen KL, Brockwell NK, Parker BS. JAK-STAT Signaling: A Double-Edged Sword of Immune Regulation and Cancer Progression. Cancers (Basel) 2019; 11:E2002. [PMID: 31842362 PMCID: PMC6966445 DOI: 10.3390/cancers11122002] [Citation(s) in RCA: 418] [Impact Index Per Article: 69.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 12/06/2019] [Accepted: 12/09/2019] [Indexed: 02/07/2023] Open
Abstract
Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling mediates almost all immune regulatory processes, including those that are involved in tumor cell recognition and tumor-driven immune escape. Antitumor immune responses are largely driven by STAT1 and STAT2 induction of type I and II interferons (IFNs) and the downstream programs IFNs potentiate. Conversely, STAT3 has been widely linked to cancer cell survival, immunosuppression, and sustained inflammation in the tumor microenvironment. The discovery of JAK-STAT cross-regulatory mechanisms, post-translational control, and non-canonical signal transduction has added a new level of complexity to JAK-STAT governance over tumor initiation and progression. Endeavors to better understand the vast effects of JAK-STAT signaling on antitumor immunity have unearthed a wide range of targets, including oncogenes, miRNAs, and other co-regulatory factors, which direct specific phenotypical outcomes subsequent to JAK-STAT stimulation. Yet, the rapidly expanding field of therapeutic developments aimed to resolve JAK-STAT aberrations commonly reported in a multitude of cancers has been marred by off-target effects. Here, we discuss JAK-STAT biology in the context of immunity and cancer, the consequences of pathway perturbations and current therapeutic interventions, to provide insight and consideration for future targeting innovations.
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Affiliation(s)
- Katie L. Owen
- Cancer Immunology and Therapeutics Programs, Peter MacCallum Cancer Centre, VIC, Melbourne 3000, Australia;
- Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Parkville 3052, Australia
| | - Natasha K. Brockwell
- Cancer Immunology and Therapeutics Programs, Peter MacCallum Cancer Centre, VIC, Melbourne 3000, Australia;
- Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Parkville 3052, Australia
| | - Belinda S. Parker
- Cancer Immunology and Therapeutics Programs, Peter MacCallum Cancer Centre, VIC, Melbourne 3000, Australia;
- Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Parkville 3052, Australia
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Xu DF, Wang LS, Zhou JH. Long non‑coding RNA CASC2 suppresses pancreatic cancer cell growth and progression by regulating the miR‑24/MUC6 axis. Int J Oncol 2019; 56:494-507. [PMID: 31894271 PMCID: PMC6959463 DOI: 10.3892/ijo.2019.4937] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 10/31/2019] [Indexed: 12/20/2022] Open
Abstract
Recent evidence indicates that the long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is involved in tumorigenesis of several types of cancer through targeting microRNAs (miRs); however, the molecular mechanism of CASC2 in pancreatic cancer remains elusive. In the present study, the expression levels of CASC2, miR-24 and mucin 6 (MUC6) were measured in pancreatic cancer specimens and cell lines by reverse transcription-quantitative PCR. Western blotting was used to determine the protein expression levels of MUC6, Integrin β4 (ITGB4), phosphorylated (p)-focal adhesion kinase (FAK) and several epithelial-to-mesenchymal transition markers in pancreatic cancer cells. MTT, colony formation, wound healing, Transwell and flow cytometry assays were performed to detect cell proliferation, colony formation, migration, invasion and apoptosis, respectively,in vitro. Morphological changes of pancreatic cancer cells were assessed by light microscopy. The interactions between CASC2, miR-24 and MUC6 were assessed by the dual-luciferase reporter assay. A tumor xenograft model was generated to investigate tumor growth in vivo. CASC2 and MUC6 were downregulated, and miR-24 was upregulated in pancreatic cancer specimens and cell lines. Functionally, CASC2 overexpression or miR-24 knockdown suppressed pancreatic cancer cell proliferation, colony formation, migration and invasion, and promoted apoptosis. Additionally, they altered cell-cell adhesion as demonstrated by the attenuated ITGB4, p-FAK and N-cadherin protein levels, as well as morphological changes. Mechanistically, CASC2 sponged miR-24 and activated its downstream target MUC6 to suppress pancreatic cancer growth and progression. CASC2 exerted tumor-suppressive functions in pancreatic cancer through the miR-24/MUC6 axis, which may be a promising target for pancreatic cancer therapy.
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Affiliation(s)
- Da-Fang Xu
- Department of Hepatic‑Biliary‑Pancreatic Center, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Li-Shan Wang
- Department of Hepatic‑Biliary‑Pancreatic Center, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
| | - Jia-Hua Zhou
- Department of Hepatic‑Biliary‑Pancreatic Center, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
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Roohallah F, Nikyar A, Milani A. The Roles and Diagnostic Potential of Long Non-Coding RNAs in Some Cancers: A Review. JOURNAL OF CLINICAL AND BASIC RESEARCH 2019. [DOI: 10.29252/jcbr.3.4.13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
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Wang L, Cho KB, Li Y, Tao G, Xie Z, Guo B. Long Noncoding RNA (lncRNA)-Mediated Competing Endogenous RNA Networks Provide Novel Potential Biomarkers and Therapeutic Targets for Colorectal Cancer. Int J Mol Sci 2019; 20:E5758. [PMID: 31744051 PMCID: PMC6888455 DOI: 10.3390/ijms20225758] [Citation(s) in RCA: 436] [Impact Index Per Article: 72.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 11/12/2019] [Accepted: 11/14/2019] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer and has a high metastasis and reoccurrence rate. Long noncoding RNAs (lncRNAs) play an important role in CRC growth and metastasis. Recent studies revealed that lncRNAs participate in CRC progression by coordinating with microRNAs (miRNAs) and protein-coding mRNAs. LncRNAs function as competitive endogenous RNAs (ceRNAs) by competitively occupying the shared binding sequences of miRNAs, thus sequestering the miRNAs and changing the expression of their downstream target genes. Such ceRNA networks formed by lncRNA/miRNA/mRNA interactions have been found in a broad spectrum of biological processes in CRC, including liver metastasis, epithelial to mesenchymal transition (EMT), inflammation formation, and chemo-/radioresistance. In this review, we summarize typical paradigms of lncRNA-associated ceRNA networks, which are involved in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the competitive crosstalk among RNA transcripts and the novel targets for CRC prognosis and therapy.
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Affiliation(s)
- Liye Wang
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX,77204, USA; (K.B.C.); (Y.L.); (G.T.); (Z.X.)
| | | | | | | | | | - Bin Guo
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX,77204, USA; (K.B.C.); (Y.L.); (G.T.); (Z.X.)
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Zhan S, Qin C, Li D, Zhao W, Nie L, Cao J, Guo J, Zhong T, Wang L, Li L, Zhang H. A Novel Long Noncoding RNA, lncR-125b, Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Sponging miR-125b. Front Genet 2019; 10:1171. [PMID: 31803241 PMCID: PMC6872680 DOI: 10.3389/fgene.2019.01171] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Accepted: 10/23/2019] [Indexed: 12/17/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) have emerged as essential regulators of skeletal myogenesis, but few myogenesis-associated lncRNAs have been identified and our understanding of their regulatory mechanisms remains limited, particularly in goat. Here, we identified a novel lncRNA, TCONS_00006810 (named lncR-125b), from our previous lncRNA sequencing data on fetal (45, 60, and 105 days of gestation, three biological replicates for each point) and postnatal (3 days after birth, n = 3) goat skeletal muscle, and found that it is highly expressed in skeletal muscle and gradually upregulated during skeletal muscle satellite cell (SMSC) differentiation in goat. Notably, overexpression of lncR-125b accelerated the expression of myogenic differentiation 1 (MyoD 1) and myogenin (MyoG), and the formation of myotubes, and knockdown of lncR-125b showed opposite effects in SMSCs. Results of dual-luciferase assay and quantitative real-time polymerase chain reaction revealed that lncR-125b acts as a molecular sponge for miR-125b and that insulin-like growth factor 2 (IGF2), a critical regulator of skeletal myogenesis, is a direct target gene of miR-125b. Further analyses showed that lncR-125b negatively regulates miR-125b expression and positively regulates IGF2 expression in SMSCs. Mechanistically, lncR-125b promotes SMSC differentiation by functioning as a competing endogenous RNA (ceRNA) for miR-125b to control IGF2 expression. These findings identify lncR-125b as a novel noncoding regulator of muscle cell differentiation and skeletal muscle development in goat.
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Affiliation(s)
- Siyuan Zhan
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Chenyu Qin
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - DanDan Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Wei Zhao
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Lu Nie
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Jiaxue Cao
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Jiazhong Guo
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.,College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Tao Zhong
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Linjie Wang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Li Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Hongping Zhang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.,College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
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Yang B, Zhou SN, Tan JN, Huang J, Chen ZT, Zhong GY, Han FH. Long Non-Coding RNA STARD13-AS Suppresses Cell Proliferation And Metastasis In Colorectal Cancer. Onco Targets Ther 2019; 12:9309-9318. [PMID: 31807011 PMCID: PMC6842744 DOI: 10.2147/ott.s217094] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 10/11/2019] [Indexed: 12/17/2022] Open
Abstract
Background Dysregulation of long non-coding RNAs (lncRNAs) is closely related with the progression of cancer in humans. The functional and regulatory roles of lncRNAs in colorectal cancer (CRC) are still largely unclear. The purpose of this study is to explore the function of lncRNA STARD13-AS in CRC. Methods The bioinformatics tool “GEPIA” was used to predict the potential expression of STARD13-AS in CRC. qRT-PCR was used to evaluate the relative expression level of STARD13-AS in CRC cells lines and tissues samples. The functional involvement of STARD13-AS in the CRC cells was assessed using MTT assay, flow cytometry, and Transwell assay. The expression levels of cyclin D, cyclin E, E-cadherin, N-cadherin, and vimentin were assessed using Western blot. Results Bioinformatics prediction and qRT-PCR results showed that STARD13-AS expression was decreased in CRC tissues. Patients with low STARD13-AS expression exhibited distant and lymphatic metastasis as well as enhancement in tumor size. STARD13-AS expression was downregulated in CRC cell lines compared to normal human colon mucosal epithelial cell line NCM460 and STARD13-AS expression in SW620 and LoVo cell lines was lowest. Moreover, we observed that while STARD13-AS overexpression suppressed the cell cycle, proliferation, migration, and invasion, while promoted apoptosis both in LoVo and SW620 cells. In addition, STARD13-AS overexpression inhibited Cyclin E, Cyclin D, N-cadherin and vimentin expression, and promoted E-cadherin expression both in LoVo and SW620 cells. Conclusion Expression of STARD13-AS suppresses cell proliferation and metastasis in CRC, suggesting that STARD13-AS might act as a potential target for CRC treatment.
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Affiliation(s)
- Bin Yang
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, People's Republic of China
| | - Sheng-Ning Zhou
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, People's Republic of China
| | - Jia-Nan Tan
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, People's Republic of China
| | - Jing Huang
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, People's Republic of China
| | - Zhi-Tao Chen
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, People's Republic of China
| | - Guang-Yu Zhong
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, People's Republic of China
| | - Fang-Hai Han
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, People's Republic of China.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen University, Guangzhou, Guangdong 510120, People's Republic of China
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Liang C, Yue C, Liang C, Ge H, Wei Z, Li G, Wu J, Huang H, Guo J. The Long Non-Coding RNA SBF2-AS1 Exerts Oncogenic Functions In Gastric Cancer By Targeting The miR-302b-3p/E2F Transcription Factor 3 Axis. Onco Targets Ther 2019; 12:8879-8893. [PMID: 31802900 PMCID: PMC6826189 DOI: 10.2147/ott.s210697] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Accepted: 09/23/2019] [Indexed: 12/27/2022] Open
Abstract
Background and aims Studies show that the long non-coding RNA, SBF2-AS1, plays a critical role in cancer progression, but the role of SBF2-AS1 in gastric cancer has not been reported. Therefore, this study aimed to elucidate the mechanism of SBF2-AS1 in gastric cancer (GC). Methods A meta-analysis, based on the gene expression omnibus database and TCGA dataset was performed to explore the prognostic value of SBF2-AS1 in GC. RT-PCR was also conducted to investigate the clinicopathologic value of SBF2-AS1 in GC. The effect of SBF2-AS1 in GC cell lines was conducted by gain or loss-of-function assays, and the SBF2-AS1 target gene was confirmed using a luciferase reporter assay and bioinformatics. Results SBF2-AS1 was overexpressed in GC tissues and cell lines, and SBF2-AS1 overexpression indicated poor overall survival and could serve as an independent prognostic factor. Moreover, knockdown of SBF2-AS1 inhibited cell growth, invasion, and metastasis, promoted apoptosis, and caused cell cycle arrest. Luciferase reporter and gain- or loss-of-function assays indicated that SBF2-AS1 acted as a competing endogenous (ceRNA) for microRNA (miR)-302b-3p, which blocked the inhibitory effect of miR-302b-3p on the E2F transcription factor 3 (E2F3). Conclusion SBF2-AS1 could be a potential diagnostic and prognostic biomarker in GC, and SBF2-AS1 accelerates tumor progression via the miR-302b-3p/E2F3 axis.
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Affiliation(s)
- Chaojie Liang
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
| | - Chaosen Yue
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China
| | - Chaowei Liang
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
| | - Hua Ge
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China
| | - Zhigang Wei
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
| | - Guangming Li
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China
| | - Jixiang Wu
- Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China
| | - He Huang
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
| | - Jiansheng Guo
- Department of General Surgery, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China
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Liu Z, Dang C, Xing E, Zhao M, Shi L, Sun J. Overexpression of CASC2 Improves Cisplatin Sensitivity in Hepatocellular Carcinoma Through Sponging miR-222. DNA Cell Biol 2019; 38:1366-1373. [PMID: 31633393 DOI: 10.1089/dna.2019.4882] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The long noncoding RNA cancer susceptibility candidate 2 (CASC2) has been shown to play a crucial role in cancer cell chemoresistance. However, its function and underlying molecular mechanism in hepatocellular carcinoma (HCC) chemoresistance remain unknown. In this study, we used cisplatin (DDP)-resistant HCC cells to investigate CASC2 function and its underlying mechanism. The results demonstrated that CASC2 expression was significantly reduced in HCC tissues and cells, especially in DDP-resistant HCC tissues and cells. Lower CASC2 expression was strongly correlated with shorter survival times in patients with HCC. Functionally, CASC2 overexpression sensitized DDP-resistant Huh7/DDP and SMMC-7721/DDP cells to DDP. Mechanically, CASC2 improved the sensitivity of HCC cells to DDP through sponging miR-222. Taken together, these findings suggested that overexpression of CASC2 overcame DDP resistance in HCC by regulating miR-222 expression, thereby providing a potential therapeutic strategy for overcoming HCC cell chemoresistance.
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Affiliation(s)
- Zhichun Liu
- Department of Hepatobiliary Surgery, The Central Hospital of Petrochina, Langfang, Hebei, P.R. China
| | - Cunshu Dang
- Department of Hepatobiliary Surgery, The Central Hospital of Petrochina, Langfang, Hebei, P.R. China
| | - Entao Xing
- Department of Hepatobiliary Surgery, The Central Hospital of Petrochina, Langfang, Hebei, P.R. China
| | - Mengjie Zhao
- Department of Hepatobiliary Surgery, The Central Hospital of Petrochina, Langfang, Hebei, P.R. China
| | - Linchang Shi
- Department of Hepatobiliary Surgery, The Central Hospital of Petrochina, Langfang, Hebei, P.R. China
| | - Jingwu Sun
- Department of Hepatobiliary Surgery, The Central Hospital of Petrochina, Langfang, Hebei, P.R. China
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Galamb O, Barták BK, Kalmár A, Nagy ZB, Szigeti KA, Tulassay Z, Igaz P, Molnár B. Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors. World J Gastroenterol 2019; 25:5026-5048. [PMID: 31558855 PMCID: PMC6747286 DOI: 10.3748/wjg.v25.i34.5026] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 07/26/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are members of the non-protein coding RNA family longer than 200 nucleotides. They participate in the regulation of gene and protein expression influencing apoptosis, cell proliferation and immune responses, thereby playing a critical role in the development and progression of various cancers, including colorectal cancer (CRC). As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality, its screening and early detection are crucial, so the identification of disease-specific biomarkers is necessary. LncRNAs are promising candidates as they are involved in carcinogenesis, and certain lncRNAs (e.g., CCAT1, CRNDE, CRCAL1-4) show altered expression in adenomas, making them potential early diagnostic markers. In addition to being useful as tissue-specific markers, analysis of circulating lncRNAs (e.g., CCAT1, CCAT2, BLACAT1, CRNDE, NEAT1, UCA1) in peripheral blood offers the possibility to establish minimally invasive, liquid biopsy-based diagnostic tests. This review article aims to describe the origin, structure, and functions of lncRNAs and to discuss their contribution to CRC development. Moreover, our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.
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Affiliation(s)
- Orsolya Galamb
- Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary
| | - Barbara K Barták
- 2nd Department of Internal Medicine, Semmelweis University, Budapest H-1088, Hungary
| | - Alexandra Kalmár
- Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary
| | - Zsófia B Nagy
- 2nd Department of Internal Medicine, Semmelweis University, Budapest H-1088, Hungary
| | - Krisztina A Szigeti
- 2nd Department of Internal Medicine, Semmelweis University, Budapest H-1088, Hungary
| | - Zsolt Tulassay
- Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary
| | - Peter Igaz
- Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary
- 2nd Department of Internal Medicine, Semmelweis University, Budapest H-1088, Hungary
| | - Béla Molnár
- Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest H-1088, Hungary
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Zhong G, Lou W, Yao M, Du C, Wei H, Fu P. Identification of novel mRNA-miRNA-lncRNA competing endogenous RNA network associated with prognosis of breast cancer. Epigenomics 2019; 11:1501-1518. [PMID: 31502865 DOI: 10.2217/epi-2019-0209] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Aim: To identify novel competing endogenous RNA (ceRNA) network related to patients prognosis in breast cancer. Materials & methods: Dysregulated mRNA based on intersection of three Gene Expression Omnibus and The Cancer Genome Atlas datasets were analyzed by bioinformatics. Results: In total 72 upregulated and 208 downregulated genes were identified. Functional analysis showed that some pathways related to cancer were significantly enriched. By means of stepwise reverse prediction and validation from mRNA to lncRNA, 19 hub genes, nine key miRNA and four key lncRNAs were identified by expression and survival analysis. Ultimately, the coexpression analysis identified RRM2-let-7a-5p-SNHG16/MAL2 as key ceRNA subnetwork associated with prognosis of breast cancer. Conclusion: We successfully constructed a novel ceRNA network, among which each component was significantly associated with breast cancer prognosis.
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Affiliation(s)
- Guansheng Zhong
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, PR China
| | - Weiyang Lou
- Program of Innovative Cancer Therapeutics, Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, College of Medicine, Key Laboratory of Organ Transplantation, Zhejiang University, 79 Qingchun Road, Zhejiang Province, Hangzhou 310003, PR China
| | - Minya Yao
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, PR China
| | - Chengyong Du
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, PR China
| | - Haiyan Wei
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, PR China
| | - Peifen Fu
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, PR China
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Chen F, Li Z, Deng C, Yan H. Integration analysis for novel lncRNA markers predicting tumor recurrence in human colon adenocarcinoma. J Transl Med 2019; 17:299. [PMID: 31470869 PMCID: PMC6717325 DOI: 10.1186/s12967-019-2049-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 08/25/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Numerous evidence has suggested that long non-coding RNA (lncRNA) acts an important role in tumor biology. This study focuses on the identification of novel prognostic lncRNA biomarkers predicting tumor recurrence in human colon adenocarcinoma. METHODS We obtained the research data from The Cancer Genome Atlas (TCGA) database. The interaction among different expressed lncRNA, miRNA and mRNA markers between colon adenocarcinoma patients with and without tumor recurrence were verified with miRcode, starBase and miRTarBase databases. We established the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network based on the verified association between the selected markers. We performed the functional enrichment analysis to obtain better understanding of the selected lncRNAs. Then we use multivariate logistic regression to identify the prognostic lncRNA markers with covariates. We also generated a nomogram predicting tumor recurrence risk based on the identified lncRNA biomarkers and clinical covariates. RESULTS We included 12,727 lncRNA, 1881 miRNA and 47,761 mRNA profiling and clinical features for 113 colon adenocarcinoma patients obtained from the TCGA database. After filtration, we used 37 specific lncRNAs, 60 miRNAs and 148 mRNAs in the ceRNA network analysis. We identified five lncRNAs as prognostic lncRNA markers predicting tumor recurrence in colon adenocarcinoma, in which four of them were identified for the first time. Finally, we generated a nomogram illustrating the association between the identified lncRNAs and the tumor recurrence risk in colon adenocarcinoma. CONCLUSIONS The four newly identified lncRNA biomarkers might be potential prognostic biomarkers predicting tumor recurrence in colon adenocarcinoma. We recommend that further clinical and fundamental researches be conducted on the identified lncRNA markers.
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Affiliation(s)
- Fangyao Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, 76 Yanta Xilu Road, Xi’an, 710061 Shaanxi China
| | - Zhe Li
- First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta Xilu Road, Xi’an, 710061 Shaanxi China
| | - Changyu Deng
- Department of Preventive Medicine, Shantou University Medical College, 22 Xinling Road, Jinping District, Shantou, 515041 Guangdong China
| | - Hong Yan
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, 76 Yanta Xilu Road, Xi’an, 710061 Shaanxi China
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Tong L, Wu W. Effects of long non-coding RNA (lncRNA) cancer susceptibility candidate 2c (CASC2c) on proliferation, metastasis and drug resistance of non-small cell lung cancer (NSCLC) cells through ERK1/2 and β-catenin signaling pathways. Pathol Res Pract 2019; 215:152522. [PMID: 31300295 DOI: 10.1016/j.prp.2019.152522] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 06/03/2019] [Accepted: 06/26/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVES This study was aimed to investigate the effects of long non-coding RNA (lncRNA) cancer susceptibility candidate 2c (CASC2c) on the proliferation, metastasis and drug resistance of non-small cell lung cancer (NSCLC) cells. METHODS The expression of CASC2c in NSCLC tissues and cell lines was detected by real-time fluorescence quantitative PCR (RT-qPCR). MTT and Transwell assay were used to determine the proliferation and migration of NSCLC cells in the experimental group and the control group respectively. The drug sensitivity test was used to confirm whether increasing the CASC2c expression level could reverse the resistance of NSCLC cells to the chemotherapy drug cisplatin. The effects of CASC2c on the expression levels of p-ERK1/2 and β-catenin were detected by western blot. RESULTS The results of RT-qPCR showed that CASC2c was under-expressed in NSCLC tissues and cells compared with normal adjacent lung tissues cells (p < 0.05). In addition, the CASC2c expression was remarkably correlated with TNM staging, tumor cell differentiation, lymph node metastasis, smoking and other pathological indicators of patients with NSCLC (p < 0.05). MTT and Transwell assay showed that the high-expression of CASC2c significantly reduced the proliferation and migration of NSCLC cells compared to that of the control group (p < 0.05). Western blot assay showed that the high-expressed CASC2c can decrease the expression of phosphorylated-ERK1/2 (p-ERK1/2) and β-catenin. CONCLUSIONS CASC2c was low expressed in NSCLC tissues and cells. What's more, it inhibited the proliferation and migration of NSCLC cells by inhibiting the expression of p-ERK1/2 and β-catenin and reversed NSCLC cells' resistance to the chemotherapy drug cisplatin. Therefore, CASC2c may serve as a new biomarker and therapeutic target in the diagnosis and treatment of NSCLC.
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Affiliation(s)
- Lingfei Tong
- Department of Pharmacy, Jiangxi Provincial People's Hospital, Aiguo Road 152, Donghu, Nanchang, Jiangxi, People's Republic of China.
| | - Wenming Wu
- Department of Pharmacy, Jiangxi Provincial People's Hospital, Aiguo Road 152, Donghu, Nanchang, Jiangxi, People's Republic of China.
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