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Qiu X, Zhang L, Guo F, Guo R. Long noncoding RNA MATN1-AS1 contributes to oxaliplatin resistance of gastric cancer cells through miR-518b/ZNF281 axis. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-03990-7. [PMID: 40072551 DOI: 10.1007/s00210-025-03990-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 02/26/2025] [Indexed: 03/14/2025]
Abstract
Chemoresistance leads to poor outcomes of patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been demonstrated as novel gene modulators in various carcinomas and chemoresistance. Our study aimed to investigate the role and underlying modulatory mechanism of lncRNA MATN1-AS1 in GC chemoresistance. CCK-8, flow cytometry, and Transwell assays were performed to explore the influence of the MATN1-AS1/microRNA (miR)-518b/zinc finger protein 281 (ZNF281) axis on the half inhibition concentration (IC50) to oxaliplatin (OXA), apoptosis, migration, and invasion of OXA-resistant GC cells. Dual-luciferase reporter assay was conducted to confirm the target association between miR-518b and MATN1-AS1 (or ZNF281). Xenograft mouse models were established to confirm the role of MATN1-AS1 silencing in vivo. The expression of MATN1-AS1, miR-518b, ZNF281, and multidrug resistance-related genes was detected through RT-qPCR and western blotting. MATN1-AS1 expression was upregulated in OXA-resistant GC tissues and cell lines versus OXA-sensitive tissues and parental cell lines. MATN1-AS1 depletion significantly inhibited the IC50 value of OXA, cell migration, invasion, and drug resistance but promoted cell apoptosis in OXA-resistant GC cells. Additionally, MATN1-AS1 upregulated ZNF281 expression by sponging miR-518b in OXA-resistant GC cells. Inhibiting miR-518b or overexpressing ZNF281 antagonized the effects of MATN1-AS1 silencing on OXA resistance of GC cells. Upregulation of ZNF281 abrogated the suppressive effects of miR-518b overexpression on OXA resistance of GC cells. Moreover, MATN1-AS1 knockdown suppressed tumor growth, OXA resistance, and Ki-67 expression in xenograft mouse models. MATN1-AS1 promotes OXA resistance of GC cells by enhancing ZNF281 expression via sequestration of miR-518b, shedding new light on the chemoresistance of GC.
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Affiliation(s)
- Xiuhuan Qiu
- Outpatient, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China
| | - Licheng Zhang
- Anesthesia Resuscitation Room, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China
| | - Fengying Guo
- Department of Tumor Radiotherapy, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.
| | - Ruixiang Guo
- Department of Tumor Radiotherapy, Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.
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Yu T, Zhao J, Li Z, Pan C, Liu J, Zheng K, Wang X, Zhang Y. Research Progress on the Role of Zinc Finger Protein in Colorectal Cancer. Cancer Rep (Hoboken) 2025; 8:e70123. [PMID: 40085529 PMCID: PMC11908617 DOI: 10.1002/cnr2.70123] [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: 05/13/2024] [Revised: 12/25/2024] [Accepted: 01/07/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND Colorectal cancer is one of the most prevalent malignancies worldwide, with a tendency of increasing incidence in developed countries, which poses a significant threat to the patients' physical and mental health. RECENT FINDINGS The process of gene transcription affects the important physiological functions of cells, so the normal expression of transcription factors is an important prerequisite for maintaining cellular homeostasis. Changes in the level of zinc finger proteins, the most prevalent transcription factor, may play an important trigger for the development of colorectal cancer. Different zinc finger proteins play different roles in terms of promoting or inhibiting cancer development. CONCLUSION This paper briefly reviews the classification, functional characteristics, and expression changes of zinc finger proteins in colorectal cancer, it focuses on how they regulate gene transcription, influence on common signaling pathways, and their potential for translational studies and clinical applications. The objective is to stimulate new ideas for their study of colorectal cancer while also providing foundational information to guide drug development and treatment strategies for colorectal cancer patients in clinical settings.
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Affiliation(s)
- Tang Yu
- The Third Affiliated Hospital of Kunming Medical UniversityKunming Medical UniversityKunmingChina
- Chongqing Nanchuan District People's HospitalChongqing Medical UniversityChongqingChina
| | - Jiumei Zhao
- Chongqing Nanchuan District People's HospitalChongqing Medical UniversityChongqingChina
| | - Ziwei Li
- Department of Gynecology and Obstetrics, Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical UniversityChongqingChina
| | - Chenglong Pan
- The Third Affiliated Hospital of Kunming Medical UniversityKunming Medical UniversityKunmingChina
| | - Jialing Liu
- The Third Affiliated Hospital of Kunming Medical UniversityKunming Medical UniversityKunmingChina
| | - Kepu Zheng
- The Third Affiliated Hospital of Kunming Medical UniversityKunming Medical UniversityKunmingChina
| | - Xiaohao Wang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
| | - Yan Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated HospitalChongqing Medical UniversityChongqingChina
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Zhang H, Tang H, Tu W, Peng F. Regulatory role of non-coding RNAs in 5-Fluorouracil resistance in gastrointestinal cancers. CANCER DRUG RESISTANCE (ALHAMBRA, CALIF.) 2025; 8:4. [PMID: 39935428 PMCID: PMC11810461 DOI: 10.20517/cdr.2024.167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/29/2024] [Accepted: 01/07/2025] [Indexed: 02/13/2025]
Abstract
Gastrointestinal (GI) cancers are becoming a growing cause of morbidity and mortality globally, posing a significant risk to human life and health. The main treatment for this kind of cancer is chemotherapy based on 5-fluorouracil (5-FU). However, the issue of 5-FU resistance is becoming increasingly prominent, which greatly limits its effectiveness in clinical treatment. Recently, numerous studies have disclosed that some non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), exert remarkable physiological functions within cells. In addition, these ncRNAs can also serve as important information communication molecules in the tumor microenvironment and regulate tumor chemotherapy resistance. In particular, they have been shown to play multiple roles in regulating 5-FU resistance in GI cancers. Herein, we summarize the targets, pathways, and mechanisms involved in regulating 5-FU resistance by ncRNAs and briefly discuss the application potential of ncRNAs as biomarkers or therapeutic targets for 5-FU resistance in GI cancers, aiming to offer a reference to tackle issues related to 5-FU resistance.
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Affiliation(s)
- Heng Zhang
- Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu 610051, Sichuan, China
- Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, Sichuan, China
| | - Hailin Tang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510700, Guangdong, China
| | - Wenling Tu
- Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, Sichuan, China
| | - Fu Peng
- Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu 610051, Sichuan, China
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Sichuan University, Chengdu 610041, Sichuan, China
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Kumar A, Yap KCH, BharathwajChetty B, Lyu J, Hegde M, Abbas M, Alqahtani MS, Khadlikar S, Zarrabi A, Khosravi A, Kumar AP, Kunnumakkara AB. Regulating the regulators: long non-coding RNAs as autophagic controllers in chronic disease management. J Biomed Sci 2024; 31:105. [PMID: 39716252 DOI: 10.1186/s12929-024-01092-9] [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: 05/31/2024] [Accepted: 10/23/2024] [Indexed: 12/25/2024] Open
Abstract
The increasing prevalence of chronic diseases and their associated morbidities demands a deeper understanding of underlying mechanism and causative factors, with the hope of developing novel therapeutic strategies. Autophagy, a conserved biological process, involves the degradation of damaged organelles or protein aggregates to maintain cellular homeostasis. Disruption of this crucial process leads to increased genomic instability, accumulation of reactive oxygen species (ROS), decreased mitochondrial functions, and suppression of ubiquitination, leading to overall decline in quality of intracellular components. Such deregulation has been implicated in a wide range of pathological conditions such as cancer, cardiovascular, inflammatory, and neurological disorders. This review explores the role of long non-coding RNAs (lncRNAs) as modulators of transcriptional and post-transcriptional gene expression, regulating diverse physiological process like proliferation, development, immunity, and metabolism. Moreover, lncRNAs are known to sequester autophagy related microRNAs by functioning as competing endogenous RNAs (ceRNAs), thereby regulating this vital process. In the present review, we delineate the multitiered regulation of lncRNAs in the autophagic dysfunction of various pathological diseases. Moreover, by highlighting recent findings on the modulation of lncRNAs in different stages of autophagy, and the emerging clinical landscape that recognizes lncRNAs in disease diagnosis and therapy, this review highlights the potential of lncRNAs as biomarkers and therapeutic targets in clinical settings of different stages of autophagic process by regulating ATG and its target genes. This focus on lncRNAs could lead to breakthroughs in personalized medicine, offering new avenues for diagnosis and treatment of complex diseases.
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Affiliation(s)
- Aviral Kumar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam, 781039, India
| | - Kenneth Chun-Hong Yap
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
- NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore
| | - Bandari BharathwajChetty
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam, 781039, India
| | - Juncheng Lyu
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
- NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore
| | - Mangala Hegde
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam, 781039, India
| | - Mohamed Abbas
- Electrical Engineering Department, College of Engineering, King Khalid University, 61421, Abha, Saudi Arabia
| | - Mohammed S Alqahtani
- Radiological Sciences Department, College of Applied Medical Sciences, King Khalid University, 61421, Abha, Saudi Arabia
- BioImaging Unit, Space Research Centre, Michael Atiyah Building, University of Leicester, Leicester, LE1 7RH, UK
| | - Soham Khadlikar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam, 781039, India
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering & Natural Sciences, Istinye University, 34396, Istanbul, Türkiye
- Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600 077, India
- Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan, 320315, Taiwan
| | - Arezoo Khosravi
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, Istanbul Okan University, 34959, Istanbul, Türkiye
| | - Alan Prem Kumar
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
- NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam, 781039, India.
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Hamdy NM, Zaki MB, Rizk NI, Abdelmaksoud NM, Abd-Elmawla MA, Ismail RA, Abulsoud AI. Unraveling the ncRNA landscape that governs colorectal cancer: A roadmap to personalized therapeutics. Life Sci 2024; 354:122946. [PMID: 39122108 DOI: 10.1016/j.lfs.2024.122946] [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: 06/19/2024] [Revised: 07/23/2024] [Accepted: 08/04/2024] [Indexed: 08/12/2024]
Abstract
Colorectal cancer (CRC) being one of the most common malignancies, has a significant death rate, especially when detected at an advanced stage. In most cases, the fundamental aetiology of CRC remains unclear despite the identification of several environmental and intrinsic risk factors. Numerous investigations, particularly in the last ten years, have indicated the involvement of epigenetic variables in this type of cancer. The development, progression, and metastasis of CRC are influenced by long non-coding RNAs (lncRNAs), which are significant players in the epigenetic pathways. LncRNAs are implicated in diverse pathological processes in CRC, such as liver metastasis, epithelial to mesenchymal transition (EMT), inflammation, and chemo-/radioresistance. It has recently been determined that CRC cells and tissues exhibit dysregulation of tens of oncogenic and tumor suppressor lncRNAs. Serum samples from CRC patients exhibit dysregulated expressions of several of these transcripts, offering a non-invasive method of detecting this kind of cancer. In this review, we outlined the typical paradigms of the deregulated lncRNA which exert significant role in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the role of lncRNAs as innovative targets for CRC prognosis and treatment.
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Affiliation(s)
- Nadia M Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abbasia Cairo, 11566, Egypt.
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia, 32897, Egypt
| | - Nehal I Rizk
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | | | - Mai A Abd-Elmawla
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Kasr Al Ainy, Cairo, 11562, Egypt
| | - Rehab A Ismail
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Ahmed I Abulsoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al Azhar University, Nasr City, Cairo, 11231, Egypt
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Dong Y, He Y, Geng Y, Wei M, Zhou X, Lian J, Hallajzadeh J. Autophagy-related lncRNAs and exosomal lncRNAs in colorectal cancer: focusing on lncRNA-targeted strategies. Cancer Cell Int 2024; 24:328. [PMID: 39342235 PMCID: PMC11439232 DOI: 10.1186/s12935-024-03503-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 09/06/2024] [Indexed: 10/01/2024] Open
Abstract
Autophagy is a cellular process that involves the degradation and recycling of cellular components, including damaged proteins and organelles. It is an important mechanism for maintaining cellular homeostasis and has been implicated in various diseases, including cancer. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that do not code for proteins but instead play regulatory roles in gene expression. Emerging evidence suggests that lncRNAs can influence autophagy and contribute to the development and progression of colorectal cancer (CRC). Several lncRNAs have been identified as key players in modulating autophagy in CRC. The dysregulation of autophagy and non-coding RNAs (ncRNAs) in CRC suggests a complex interplay between these two factors in the pathogenesis of the disease. Modulating autophagy may sensitize cancer cells to existing therapies or improve the efficacy of new treatment approaches. Additionally, targeting specific lncRNAs involved in autophagy regulation could potentially be used as a therapeutic intervention to inhibit tumor growth, metastasis, and overcome drug resistance in CRC. In this review, a thorough overview is presented, encompassing the functions and underlying mechanisms of autophagy-related lncRNAs in a range of critical areas within tumor biology. These include cell proliferation, apoptosis, migration, invasion, drug resistance, angiogenesis, and radiation resistance.
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Affiliation(s)
- Yan Dong
- The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050011, Hebei, China
| | - Yiwei He
- The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050011, Hebei, China
| | - Yanna Geng
- The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050011, Hebei, China
| | - Meimei Wei
- The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050011, Hebei, China
| | - Xiaomei Zhou
- The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050011, Hebei, China
| | - Jianlun Lian
- The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, 050011, Hebei, China.
| | - Jamal Hallajzadeh
- Department of Biochemistry and Nutrition, Research Center for Evidence-Based Health Management, Maragheh University of Medical Sciences, Maragheh, Iran.
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Kim D, Go SH, Song Y, Lee DK, Park JR. Decursin Induces G1 Cell Cycle Arrest and Apoptosis through Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress in Human Colorectal Cancer Cells in In Vitro and Xenograft Models. Int J Mol Sci 2024; 25:9939. [PMID: 39337425 PMCID: PMC11432441 DOI: 10.3390/ijms25189939] [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: 08/26/2024] [Revised: 09/12/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Decursin, a coumarin isolated from Angelica gigas Nakai, possesses anti-inflammatory and anti-cancer properties. However, the molecular mechanisms underlying its anti-cancer effects against human colorectal cancer (CRC) are unclear. Therefore, this study aimed to evaluate the biological activities of decursin in CRC in vitro and in vivo and to determine its underlying mechanism of action. Decursin exhibited anti-tumor activity in vitro, accompanied by an increase in G1 cell cycle arrest and apoptosis in HCT-116 and HCT-8 CRC cells. Decursin also induced the production of reactive oxygen species (ROS), thereby activating the endoplasmic reticulum (ER) stress apoptotic pathway in CRC cells. Furthermore, the role of ROS in decursin-induced apoptosis was investigated using the antioxidant N-acetyl-L-cysteine. Inhibiting ROS production reversed decursin-induced ER stress. Moreover, decursin significantly suppressed tumor growth in a subcutaneous xenograft mouse model of HCT-116 and HCT-8 CRC cells without causing host toxicity. Decursin also decreased cell proliferation, as documented by Ki-67, and partly increased cleaved caspase 3 expression in tumor tissues by activating ER stress apoptotic pathways. These findings suggest that decursin induces cell cycle arrest and apoptosis in human CRC cells via ROS-mediated ER stress, suggesting that decursin could be a therapeutic agent for CRC.
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Affiliation(s)
| | | | | | - Dong-Keon Lee
- Division of Research Center, Scripps Korea Antibody Institute, Chuncheon 24341, Republic of Korea; (D.K.); (S.-H.G.); (Y.S.)
| | - Jeong-Ran Park
- Division of Research Center, Scripps Korea Antibody Institute, Chuncheon 24341, Republic of Korea; (D.K.); (S.-H.G.); (Y.S.)
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Yu JM, Sun CQ, Xu HH, Jiang YL, Jiang XY, Ni SQ, Zhao TY, Liu LX. Navigating the labyrinth of long non-coding RNAs in colorectal cancer: From chemoresistance to autophagy. World J Gastrointest Oncol 2024; 16:3376-3381. [PMID: 39171173 PMCID: PMC11334040 DOI: 10.4251/wjgo.v16.i8.3376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/03/2024] [Accepted: 05/22/2024] [Indexed: 08/07/2024] Open
Abstract
Long non-coding RNAs (lncRNAs), with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity, have been found to impact colorectal cancer (CRC) through various biological processes. LncRNA expression can regulate autophagy, which plays dual roles in the initiation and progression of cancers, including CRC. Abnormal expression of lncRNAs is associated with the emergence of chemoresistance. Moreover, it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance. Two recent studies titled "Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506" and "Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription" revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC, respectively. In this editorial, we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.
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Affiliation(s)
- Jia-Mei Yu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Chong-Qi Sun
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Huan-Huan Xu
- Department of Hematology and Oncology, Department of Geriatric Lung Cancer Research Laboratory, Jiangsu Province Geriatric Hospital, Nanjing 210009, Jiangsu Province, China
| | - Ya-Li Jiang
- Central Laboratory, The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Ili & Jiangsu Joint Institute of Health, Yining 835000, Xinjiang Uyghur Autonomous Region, China
| | - Xing-Yu Jiang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Si-Qi Ni
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Ting-Yu Zhao
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Ling-Xiang Liu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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Yu Z, Hu MY, Dai J. LncRNA GAS5-AS1 regulates colorectal cancer cell proliferation, migration, and invasion by targeting miR-106a-5p. WORLD CHINESE JOURNAL OF DIGESTOLOGY 2024; 32:525-533. [DOI: 10.11569/wcjd.v32.i7.525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2024]
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10
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Liu M, Jiang H, Momeni MR. Epigenetic regulation of autophagy by non-coding RNAs and exosomal non-coding RNAs in colorectal cancer: A narrative review. Int J Biol Macromol 2024; 273:132732. [PMID: 38823748 DOI: 10.1016/j.ijbiomac.2024.132732] [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: 03/18/2024] [Revised: 05/16/2024] [Accepted: 05/19/2024] [Indexed: 06/03/2024]
Abstract
One of the major diseases affecting people globally is colorectal cancer (CRC), which is primarily caused by a lack of effective medical treatment and a limited understanding of its underlying mechanisms. Cellular autophagy functions to break down and eliminate superfluous proteins and substances, thereby facilitating the continual replacement of cellular elements and generating vital energy for cell processes. Non-coding RNAs and exosomal ncRNAs have a crucial impact on regulating gene expression and essential cellular functions such as autophagy, metastasis, and treatment resistance. The latest research has indicated that specific ncRNAs and exosomal ncRNA to influence the process of autophagy in CRC cells, which could have significant consequences for the advancement and treatment of this disease. It has been determined that a variety of ncRNAs have a vital function in regulating the genes essential for the formation and maturation of autophagosomes. Furthermore, it has been confirmed that ncRNAs have a considerable influence on the signaling pathways associated with autophagy, such as those involving AMPK, AKT, and mTOR. Additionally, numerous ncRNAs have the potential to affect specific genes involved in autophagy. This study delves into the control mechanisms of ncRNAs and exosomal ncRNAs and examines how they simultaneously influence autophagy in CRC.
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Affiliation(s)
- Minghua Liu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110000, Liaoning, China
| | - Hongfang Jiang
- Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang 110000, Liaoning, China.
| | - Mohammad Reza Momeni
- University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.
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Khalafizadeh A, Hashemizadegan SD, Shokri F, Bakhshinejad B, Jabbari K, Motavaf M, Babashah S. Competitive endogenous RNA networks: Decoding the role of long non-coding RNAs and circular RNAs in colorectal cancer chemoresistance. J Cell Mol Med 2024; 28:e18197. [PMID: 38506091 PMCID: PMC10951891 DOI: 10.1111/jcmm.18197] [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: 06/08/2023] [Revised: 11/17/2023] [Accepted: 02/04/2024] [Indexed: 03/21/2024] Open
Abstract
Colorectal cancer (CRC) is recognized as one of the most common gastrointestinal malignancies across the globe. Despite significant progress in designing novel treatments for CRC, there is a pressing need for more effective therapeutic approaches. Unfortunately, many patients undergoing chemotherapy develop drug resistance, posing a significant challenge for cancer treatment. Non-coding RNAs (ncRNAs) have been found to play crucial roles in CRC development and its response to chemotherapy. However, there are still gaps in our understanding of interactions among various ncRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs). These ncRNAs can act as either oncogenes or tumour suppressors, affecting numerous biological functions in different cancers including CRC. A class of ncRNA molecules known as competitive endogenous RNAs (ceRNAs) has emerged as a key player in various cellular processes. These molecules form networks through lncRNA/miRNA/mRNA and circRNA/miRNA/mRNA interactions. In CRC, dysregulation of ceRNA networks has been observed across various cellular processes, including proliferation, apoptosis and angiogenesis. These dysregulations are believed to play a significant role in the progression of CRC and, in certain instances, may contribute to the development of chemoresistance. Enriching our knowledge of these dysregulations holds promise for advancing the field of diagnostic and therapeutic modalities for CRC. In this review, we discuss lncRNA- and circRNA-associated ceRNA networks implicated in the emergence and advancement of drug resistance in colorectal carcinogenesis.
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Affiliation(s)
- Ali Khalafizadeh
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
| | | | - Fatemeh Shokri
- Research and Development Center of BiotechnologyTarbiat Modares UniversityTehranIran
| | - Babak Bakhshinejad
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
| | - Keyvan Jabbari
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
| | - Mahsa Motavaf
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
| | - Sadegh Babashah
- Department of Molecular Genetics, Faculty of Biological SciencesTarbiat Modares UniversityTehranIran
- Research and Development Center of BiotechnologyTarbiat Modares UniversityTehranIran
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12
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Zhang Y, Tang J, Wang C, Zhang Q, Zeng A, Song L. Autophagy-related lncRNAs in tumor progression and drug resistance: A double-edged sword. Genes Dis 2024; 11:367-381. [PMID: 37588204 PMCID: PMC10425854 DOI: 10.1016/j.gendis.2023.04.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/21/2023] [Accepted: 04/23/2023] [Indexed: 08/18/2023] Open
Abstract
The incidence and mortality rates of cancer are increasing every year worldwide but the survival rate of cancer patients is still unsatisfactory. Therefore, it is necessary to further elucidate the molecular mechanisms involved in tumor development and drug resistance to improve cancer cure or survival rates. In recent years, autophagy has become a hot topic in the field of oncology research, which plays a double-edged role in tumorigenesis, progression, and drug resistance. Meanwhile, long non-coding RNA (lncRNA) has also been shown to regulate autophagy, and the two-sided nature of autophagy determines the dual regulatory role of autophagy-related lncRNAs (ARlncRNAs). Therefore, ARlncRNAs can be effective therapeutic targets for various cancers. Furthermore, the high abundance and stability of ARlncRNAs in tumor tissues make them promising biomarkers. In this review, we summarized the roles and mechanisms of ARlncRNAs in tumor cell proliferation, apoptosis, migration, invasion, drug resistance, angiogenesis, radiation resistance, and immune regulation. In addition, we described the clinical significance of these ARlncRNAs, including as biomarkers/therapeutic targets and their association with clinical drugs.
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Affiliation(s)
- Yunchao Zhang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China
| | - Jiayu Tang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China
| | - Cheng Wang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China
| | - Qinxiu Zhang
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China
| | - Anqi Zeng
- Institute of Translational Pharmacology and Clinical Application, Sichuan Academy of Chinese Medical Science, Chengdu, Sichuan 610041, China
| | - Linjiang Song
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China
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13
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Ying Z, Wenjing S, Jing B, Songbin F, Kexian D. Advances in long non-coding RNA regulating drug resistance of cancer. Gene 2023; 887:147726. [PMID: 37625566 DOI: 10.1016/j.gene.2023.147726] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 06/19/2023] [Accepted: 08/21/2023] [Indexed: 08/27/2023]
Abstract
Drug resistance is one of the main challenges in cancer treatment. Long non coding RNAs (lncRNAs) play a complex and precise regulatory role in regulating drug resistance of cancer. The common ways of lncRNA regulating drug resistance of cancer involve ATP binding transporter overexpression, abnormal DNA damage response, tumor cell apoptosis, accumulation of epithelial mesenchymal transformation and cancer stem cell formation. Moreover, studies on exosomal lncRNAs regulating cancer drug resistance are developed in recent years. Further study on the role and mechanism of lncRNAs drug resistance in cancer will help clinical cancer treatment program and explore new treatment methods. This paper reviews recent advances in lncRNAs regulating drug resistance of cancer, especially the role of exosomal lncRNAs.
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Affiliation(s)
- Zhang Ying
- Key laboratory of preservation of human genetic resources and disease control in China, Harbin Medical University, Ministry of Education, Harbin 150081, China; Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China
| | - Sun Wenjing
- Key laboratory of preservation of human genetic resources and disease control in China, Harbin Medical University, Ministry of Education, Harbin 150081, China; Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China
| | - Bai Jing
- Key laboratory of preservation of human genetic resources and disease control in China, Harbin Medical University, Ministry of Education, Harbin 150081, China; Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China
| | - Fu Songbin
- Key laboratory of preservation of human genetic resources and disease control in China, Harbin Medical University, Ministry of Education, Harbin 150081, China; Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China
| | - Dong Kexian
- Key laboratory of preservation of human genetic resources and disease control in China, Harbin Medical University, Ministry of Education, Harbin 150081, China; Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China.
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14
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Saadh MJ, Almoyad MAA, Arellano MTC, Maaliw RR, Castillo-Acobo RY, Jalal SS, Gandla K, Obaid M, Abdulwahed AJ, Ibrahem AA, Sârbu I, Juyal A, Lakshmaiya N, Akhavan-Sigari R. Long non-coding RNAs: controversial roles in drug resistance of solid tumors mediated by autophagy. Cancer Chemother Pharmacol 2023; 92:439-453. [PMID: 37768333 DOI: 10.1007/s00280-023-04582-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 08/12/2023] [Indexed: 09/29/2023]
Abstract
Current genome-wide studies have indicated that a great number of long non-coding RNAs (lncRNAs) are transcribed from the human genome and appeared as crucial regulators in a variety of cellular processes. Many studies have displayed a significant function of lncRNAs in the regulation of autophagy. Autophagy is a macromolecular procedure in cells in which intracellular substrates and damaged organelles are broken down and recycled to relieve cell stress resulting from nutritional deprivation, irradiation, hypoxia, and cytotoxic agents. Autophagy can be a double-edged sword and play either a protective or a damaging role in cells depending on its activation status and other cellular situations, and its dysregulation is related to tumorigenesis in various solid tumors. Autophagy induced by various therapies has been shown as a unique mechanism of resistance to anti-cancer drugs. Growing evidence is showing the important role of lncRNAs in modulating drug resistance via the regulation of autophagy in a variety of cancers. The role of lncRNAs in drug resistance of cancers is controversial; they may promote or suppress drug resistance via either activation or inhibition of autophagy. Mechanisms by which lncRNAs regulate autophagy to affect drug resistance are different, mainly mediated by the negative regulation of micro RNAs. In this review, we summarize recent studies that investigated the role of lncRNAs/autophagy axis in drug resistance of different types of solid tumors.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
- Applied Science Research Center, Applied Science Private University, Amman, 11831, Jordan
| | | | | | - Renato R Maaliw
- College of Engineering, Southern Luzon State University, Lucban, Quezon, Philippines
| | | | - Sarah Salah Jalal
- College of Nursing, National University of Science and Technology, Dhi Qar, Iraq
| | - Kumaraswamy Gandla
- Department of Pharmaceutical Analysis, University of Chaitanya, Hanamkonda, India
| | | | | | - Azher A Ibrahem
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
| | - Ioan Sârbu
- 2nd Department of Surgery-Pediatric Surgery and Orthopedics, "Grigore T. Popa" University of Medicine and Pharmacy, 700115, Iași, Romania.
| | - Ashima Juyal
- Department of Electronics & Communication Engineering, Uttaranchal Institute of Technology, Uttaranchal University, Dehradun, 248007, India
| | - Natrayan Lakshmaiya
- Department of Mechanical Engineering, Saveetha School of Engineering, SIMATS, Chennai, Tamil Nadu, India
| | - Reza Akhavan-Sigari
- Department of Neurosurgery, University Medical Center Tuebingen, Tübingen, Germany
- Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Warsaw, Poland
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15
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Ebrahimi N, Hakimzadeh A, Bozorgmand F, Speed S, Manavi MS, Khorram R, Farahani K, Rezaei-Tazangi F, Mansouri A, Hamblin MR, Aref AR. Role of non-coding RNAs as new therapeutic targets in regulating the EMT and apoptosis in metastatic gastric and colorectal cancers. Cell Cycle 2023; 22:2302-2323. [PMID: 38009668 PMCID: PMC10730205 DOI: 10.1080/15384101.2023.2286804] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 05/11/2023] [Accepted: 08/01/2023] [Indexed: 11/29/2023] Open
Abstract
Colorectal cancer (CRC) and gastric cancer (GC), are the two most common cancers of the gastrointestinal tract, and are serious health concerns worldwide. The discovery of more effective biomarkers for early diagnosis, and improved patient prognosis is important. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), can regulate cellular processes such as apoptosis and the epithelial-mesenchymal transition (EMT) leading to progression and resistance of GC and CRC tumors. Moreover these pathways (apoptosis and EMT) may serve as therapeutic targets, to prevent metastasis, and to overcome drug resistance. A subgroup of ncRNAs is common to both GC and CRC tumors, suggesting that they might be used as biomarkers or therapeutic targets. In this review, we highlight some ncRNAs that can regulate EMT and apoptosis as two opposite mechanisms in cancer progression and metastasis in GC and CRC. A better understanding of the biological role of ncRNAs could open up new avenues for the development of personalized treatment plans for GC and CRC patients.
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Affiliation(s)
- Nasim Ebrahimi
- Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Isfahan, Iran
| | - Ali Hakimzadeh
- Department of Medical Biotechnologies, University of Siena, Tuscany, Italy
| | - Farima Bozorgmand
- Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Sepehr Speed
- Medical Campus, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | | | - Roya Khorram
- Bone and Joint Diseases Research Center, Department of Orthopedic Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kobra Farahani
- Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
| | - Fatemeh Rezaei-Tazangi
- Department of Anatomy, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Atena Mansouri
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Reza Aref
- Xsphera Biosciences, Translational Medicine group, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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16
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Lin W, Mo CQ, Kong LJ, Chen L, Wu KL, Wu X. FTO-mediated epigenetic upregulation of LINC01559 confers cell resistance to docetaxel in breast carcinoma by suppressing miR-1343-3p. Kaohsiung J Med Sci 2023; 39:873-882. [PMID: 37584416 DOI: 10.1002/kjm2.12728] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 04/27/2023] [Accepted: 06/04/2023] [Indexed: 08/17/2023] Open
Abstract
This study was to explore the regulatory effect of long non-coding RNA LINC01559 on Docetaxel resistance in breast carcinoma (BCa) and its underlying mechanism. In the present study, we found that LINC01559 expression was elevated and LINC01559 overexpression facilitated docetaxel resistance in BCa cells. Moreover, it was revealed that the upregulation of LINC01559 in BCa cells was induced by FTO-mediated demethylation in an m6A-YTHDF2-dependent manner. Additionally, Dual-luciferase reporter assay confirmed the binding ability between LINC01559 and miR-1343-3p, and Pearson correlation analysis showed a negative correlation between them. Particularly, miR-1343-3p inhibition partly abolished the suppression on docetaxel resistance in BCa cells caused by LINC01559 knockdown. To sum up, FTO-mediated epigenetic upregulation of LINC01559 promoted cell resistance to Docetaxel in BCa by negatively regulating miR-1343-3p.
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Affiliation(s)
- Wei Lin
- Department of Thyroid and Breast Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Cai-Qin Mo
- Department of Thyroid and Breast Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Ling-Jun Kong
- Department of Thyroid and Breast Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Ling Chen
- Department of Thyroid and Breast Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Kun-Lin Wu
- Department of Thyroid and Breast Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Xian Wu
- Department of Thyroid and Breast Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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17
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Landry J, Shows K, Jagdeesh A, Shah A, Pokhriyal M, Yakovlev V. Regulatory miRNAs in cancer cell recovery from therapy exposure and its implications as a novel therapeutic strategy for preventing disease recurrence. Enzymes 2023; 53:113-196. [PMID: 37748835 DOI: 10.1016/bs.enz.2023.07.007] [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] [Indexed: 09/27/2023]
Abstract
The desired outcome of cancer therapies is the eradication of disease. This can be achieved when therapy exposure leads to therapy-induced cancer cell death as the dominant outcome. Theoretically, a permanent therapy-induced growth arrest could also contribute to a complete response, which has the potential to lead to remission. However, preclinical models have shown that therapy-induced growth arrest is not always durable, as recovering cancer cell populations can contribute to the recurrence of cancer. Significant research efforts have been expended to develop strategies focusing on the prevention of recurrence. Recovery of cells from therapy exposure can occur as a result of several cell stress adaptations. These include cytoprotective autophagy, cellular quiescence, a reversable form of senescence, and the suppression of apoptosis and necroptosis. It is well documented that microRNAs regulate the response of cancer cells to anti-cancer therapies, making targeting microRNAs therapeutically a viable strategy to sensitization and the prevention of recovery. We propose that the use of microRNA-targeting therapies in prolonged sequence, that is, a significant period after initial therapy exposure, could reduce toxicity from the standard combination strategy, and could exploit new epigenetic states essential for cancer cells to recover from therapy exposure. In a step toward supporting this strategy, we survey the available scientific literature to identify microRNAs which could be targeted in sequence to eliminate residual cancer cell populations that were arrested as a result of therapy exposure. It is our hope that by successfully identifying microRNAs which could be targeted in sequence we can prevent disease recurrence.
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Affiliation(s)
- Joseph Landry
- Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, United States.
| | - Kathryn Shows
- Department of Biology, Virginia State University, Petersburg, VA, United States
| | - Akash Jagdeesh
- Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, United States
| | - Aashka Shah
- Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, United States
| | - Mihir Pokhriyal
- Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, United States
| | - Vasily Yakovlev
- Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA, United States.
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18
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Kumar A, Girisa S, Alqahtani MS, Abbas M, Hegde M, Sethi G, Kunnumakkara AB. Targeting Autophagy Using Long Non-Coding RNAs (LncRNAs): New Landscapes in the Arena of Cancer Therapeutics. Cells 2023; 12:cells12050810. [PMID: 36899946 PMCID: PMC10000689 DOI: 10.3390/cells12050810] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 02/04/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Cancer has become a global health hazard accounting for 10 million deaths in the year 2020. Although different treatment approaches have increased patient overall survival, treatment for advanced stages still suffers from poor clinical outcomes. The ever-increasing prevalence of cancer has led to a reanalysis of cellular and molecular events in the hope to identify and develop a cure for this multigenic disease. Autophagy, an evolutionary conserved catabolic process, eliminates protein aggregates and damaged organelles to maintain cellular homeostasis. Accumulating evidence has implicated the deregulation of autophagic pathways to be associated with various hallmarks of cancer. Autophagy exhibits both tumor-promoting and suppressive effects based on the tumor stage and grades. Majorly, it maintains the cancer microenvironment homeostasis by promoting viability and nutrient recycling under hypoxic and nutrient-deprived conditions. Recent investigations have discovered long non-coding RNAs (lncRNAs) as master regulators of autophagic gene expression. lncRNAs, by sequestering autophagy-related microRNAs, have been known to modulate various hallmarks of cancer, such as survival, proliferation, EMT, migration, invasion, angiogenesis, and metastasis. This review delineates the mechanistic role of various lncRNAs involved in modulating autophagy and their related proteins in different cancers.
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Affiliation(s)
- Aviral Kumar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati 781039, Assam, India
| | - Sosmitha Girisa
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati 781039, Assam, India
| | - Mohammed S. Alqahtani
- Radiological Sciences Department, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia
- BioImaging Unit, Space Research Centre, Michael Atiyah Building, University of Leicester, Leicester LE1 7RH, UK
| | - Mohamed Abbas
- Electrical Engineering Department, College of Engineering, King Khalid University, Abha 61421, Saudi Arabia
- Electronics and Communications Department, College of Engineering, Delta University for Science and Technology, Gamasa 35712, Egypt
| | - Mangala Hegde
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati 781039, Assam, India
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
- NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
- Correspondence: (G.S.); (A.B.K.); Tel.: +91-789-600-5326 (G.S.); +91-361-258-2231 (A.B.K.)
| | - Ajaikumar B. Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati 781039, Assam, India
- Correspondence: (G.S.); (A.B.K.); Tel.: +91-789-600-5326 (G.S.); +91-361-258-2231 (A.B.K.)
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19
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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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20
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Chen LJ, Chen X, Niu XH, Peng XF. LncRNAs in colorectal cancer: Biomarkers to therapeutic targets. Clin Chim Acta 2023; 543:117305. [PMID: 36966964 DOI: 10.1016/j.cca.2023.117305] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/18/2023] [Accepted: 03/20/2023] [Indexed: 03/29/2023]
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related death in men and women worldwide. As early detection is associated with lower mortality, novel biomarkers are urgently needed for timely diagnosis and appropriate management of patients to achieve the best therapeutic response. Long noncoding RNAs (lncRNAs) have been reported to play essential roles in CRC progression. Accordingly, the regulatory roles of lncRNAs should be better understood in general and for identifying diagnostic, prognostic and predictive biomarkers in CRC specifically. In this review, the latest advances on the potential diagnostic and prognostic lncRNAs as biomarkers in CRC samples were highlighted, Current knowledge on dysregulated lncRNAs and their potential molecular mechanisms were summarized. The potential therapeutic implications and challenges for future and ongoing research in the field were also discussed. Finally, novel insights on the underlying mechanisms of lncRNAs were examined as to their potential role as biomarkers and therapeutic targets in CRC. This review may be used to design future studies and advanced investigations on lncRNAs as biomarkers for the diagnosis, prognosis and therapy in CRC.
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Affiliation(s)
- Ling-Juan Chen
- Department of Clinical Laboratory, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Xiang Chen
- Department of General Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Xiao-Hua Niu
- Department of General Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Xiao-Fei Peng
- Department of General Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China.
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21
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Sun CC, Li L, jiang ZC, Liu ZC, Wang L, Wang HJ. The Functional Role of LncRNA UCA1 in Pancreatic Cancer: a mini-review. J Cancer 2023; 14:275-280. [PMID: 36741256 PMCID: PMC9891880 DOI: 10.7150/jca.79171] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 12/25/2022] [Indexed: 01/11/2023] Open
Abstract
Pancreatic cancer (PaC) is a common malignant tumor of the digestive tract, with a 5-year survival rate of less than 5% and high mortality rate in the world. LncRNAs have been showed to possess multiple biological functions in growth, differentiation, and proliferation, which play an important role in different biological processes and diseases, especially in the development of tumors. LncRNA UCA1, which is firstly identified in human bladder cancer, has been showed to be a tumor promoter in pancreatic cancer. Recent researches have showed that UCA1 might promote pancreatic carcinogenesis and progression, and correlate with drug resistance. In this review, we address the biological function and regulatory mechanism of UCA1 in pancreatic cancer, which might give a new approach for clinical diagnosis and treatment.
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Affiliation(s)
- Cen-Cen Sun
- Basic Medical Experimental Teaching Center, Zhejiang University, Hangzhou 310030, Zhejiang, China
| | - Li Li
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.,Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
| | - Zhi-Chen jiang
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
| | - Zheng-Chuang Liu
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.,Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
| | - Liang Wang
- Center for Plastic and Reconstructive Surgery, Department of Hand and Reconstruction Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.,✉ Corresponding authors: Hui-Ju Wang, E-mail: ; Liang Wang, E-mail:
| | - Hui-Ju Wang
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.,Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.,✉ Corresponding authors: Hui-Ju Wang, E-mail: ; Liang Wang, E-mail:
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22
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Karimpur Zahmatkesh A, Moqadami A, Khalaj- Kondori M. Insights into the radiotherapy-induced deferentially expressed RNAs in colorectal cancer management. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2023; 26:1380-1389. [PMID: 37970448 PMCID: PMC10634048 DOI: 10.22038/ijbms.2023.71259.15482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 07/02/2023] [Indexed: 11/17/2023]
Abstract
Radiotherapy (RT) has been commonly applied to treat advanced local cancers. In radiation therapy, high doses of radiation are utilized to trigger cell death. Radiation often leads to DNA double-strand breakages (DSB), which causes the activation of downstream genes including those for non-coding RNAs (ncRNA) such as long non-coding and RNAsmicro RNAs. The consequence of RT significantly relies on the radiosensitivity of cancer cells, which is affected by multiple factors, including some proteins and cellular processes. Activation of these genes can cause cell cytotoxicity and indirectly damages the cells. Recent studies have shown that non-coding RNAs can play as radiosensitivity or radioinhibitory regulators in cancers by mechanisms such as cell cycle arrest or affecting the DNA damage repair systems. ncRNAs are also known to function as tumor suppressor genes or oncogenes in colorectal cancer and therefore are considered potential diagnostic biomarkers in disease detection. For example, the investigations have shown that miR-29a and miR-224 can be informative biomarkers for early detection or screening of CRC via a noninvasive method such as liquid biopsy. Here, we discuss ncRNAs involved in the radioresistance and radiosensitivity of CRC and highlight their predictive clinical value in response to RT. Accordingly, this review represents a principal guide in the context of three major types of ncRNAs with potential roles in the pathway of radiosensitivity and radioresistance, including miRNAs, lncRNAs, and circRNAs which can be considered a precious archivement in organizing additional studies and broadening views in this area. Our findings can also assist radiotherapists in predicting CRC patients' response and, therefore, prognosis to radiation therapy, although, to achieve our goals in the clinic, we certainly need further studies.
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Affiliation(s)
- Arezu Karimpur Zahmatkesh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
- These authors contributed eqully to this work
| | - Amin Moqadami
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
- These authors contributed eqully to this work
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Lu C, Ge T, Shao Y, Cui W, Li Z, Xu W, Bao X. ZNF281 drives hepatocyte senescence in alcoholic liver disease by reducing HK2-stabilized PINK1/Parkin-mediated mitophagy. Cell Prolif 2022; 56:e13378. [PMID: 36514923 PMCID: PMC9977663 DOI: 10.1111/cpr.13378] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/20/2022] [Accepted: 11/28/2022] [Indexed: 12/15/2022] Open
Abstract
We investigated the role of zinc-finger protein 281 (ZNF281), a novel molecule, in ethanol-induced hepatocyte senescence and uncovered the potential mechanism. Real-time PCR, Western blot, immunofluorescence staining, and enzyme-linked immunosorbent assay were performed to explore the role of ZNF281 in hepatocyte senescence. ZNF281 expression was upregulated in both alcohol-fed mice livers and ethanol-treated hepatocytes. Silence of ZNF281 in hepatocytes using siRNA mitigated ethanol-caused decrease in cell viability and increased release of aspartate aminotransferase, alanine transaminase, and lactate dehydrogenase. ZNF281 siRNA reduced senescence-associated β-galactosidase-positive cells under ethanol exposure, abolished cell cycle arrest at G0/G1 phase, and diminished senescence-associated secretory phenotype and proinflammatory cytokines (IL-1β and IL-6) release. At molecular level, ZNF281 deficiency altered the expression profile of senescence-associated proteins including p53, p21, p16, high mobility group AT-hook 1, and phospho-histone H2A.X and telomerase-associated regulatory factors including telomerase reverse transcriptase, telomeric repeat binding factor 1 (TRF1), and TRF2. ZNF281 knockdown promoted hepatocyte recovery from ethanol-induced mitochondrial dysfunction and ROS production, which was correlated with rescuing HK2-PINK1/Parkin signalling-mediated mitophagy. Mechanistically, ZNF281 directly bound to 5'-GGCGGCGGGCGG-3' motif within HK2 promoter region and transcriptionally repressed HK2 expression. Systematic ZNF281 knockdown by adeno-associated virus encoding ZNF281 shRNA protected mice from alcohol feeding-caused hepatocyte injury and senescence. This study provides a novel factor ZNF281 as a driver of hepatocyte senescence during alcoholic liver disease.
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Affiliation(s)
- Chunfeng Lu
- School of PharmacyNantong UniversityNantongChina
| | - Ting Ge
- School of PharmacyNantong UniversityNantongChina
| | - Yunyun Shao
- School of PharmacyNantong UniversityNantongChina
| | - Wenqian Cui
- School of PharmacyNantong UniversityNantongChina
| | - Zhe Li
- School of PharmacyNantong UniversityNantongChina
| | - Wenxuan Xu
- School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingChina
| | - Xiaofeng Bao
- School of PharmacyNantong UniversityNantongChina
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Huang G, Cai G, Hu D, Li J, Xu Q, Chen Z, Xu B. Low SP1 SUMOylation-dependent SNHG17 upregulation promotes drug resistance of gastric cancer through impairing hsa-miR-23b-3p-induced Notch2 inhibition. Cell Oncol (Dordr) 2022; 45:1329-1346. [PMID: 36214997 DOI: 10.1007/s13402-022-00722-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2022] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE Specificity protein 1 (SP1), a transcription factor mediated by SUMOylation modifiers, is upregulated in gastric cancer (GC) and shares negative correlation with patient prognosis. Here, we paid main attention to the role of SP1 SUMOylation in the drug resistance of GC cells and the possible long non-coding RNA (lncRNA) SNHG17/microRNA-23b-3p (miR-23b-3p)/Notch2 network engaged in this process. METHODS Tumor tissues and non-tumor tissues were isolated from GC patients who received treatment with capecitabine and cisplatin (DDP). Co-immunoprecipitation was utilized to detect the SUMOylation level of SP1. Using gain- and loss-of-function approaches, we assessed the impacts of SNHG17/miR-23b-3p/Notch2 on sensitivity of DDP-resistant GC cells in vitro and in vivo. A series of assays such as luciferase activity detection and RNA pull-down were conducted for mechanistic exploration. RESULTS SP1 expression was increased due to low SP1 SUMOylation level in the recurrent GC tissues. This increase led to upregulated SNHG17 expression and SP1 binding sites existed in the SNHG17 promoter. In addition, SNHG17 could bind to miR-23b-3p while miR-23b-3p targeted Notch2. Loss of SNHG17 reduced the resistance of DDP-resistant GC cells to DDP, which was achieved through miR-23b-3p-dependent Notch2 inhibition. Finally, SP1 silencing attenuated the resistance of GC to DDP in mice. CONCLUSION Low SP1 SUMOylation induces SNHG17 upregulation and blocks miR-23b-3p-induced Notch2 inhibition, contributing to the resistance of GC to DDP. This study may aid in the development of therapeutic targets overcoming the chemoresistance of GC.
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Affiliation(s)
- Guoyu Huang
- Department of AnoRectal Surgery, Hainan General Hospital, Hainan, 570105, Haikou, People's Republic of China
| | - Guohao Cai
- Department of AnoRectal Surgery, Hainan General Hospital, Hainan, 570105, Haikou, People's Republic of China
| | - Dongwei Hu
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Jinjie Li
- Department of Hepato-pancreato-biliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, South Baixiang Street, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Qigang Xu
- Department of Hepato-pancreato-biliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, South Baixiang Street, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Zongjing Chen
- Department of Hepato-pancreato-biliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, South Baixiang Street, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Bo Xu
- Department of Hepato-pancreato-biliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, South Baixiang Street, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China.
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Roh J, Im M, Chae Y, Kang J, Kim W. The Involvement of Long Non-Coding RNAs in Glutamine-Metabolic Reprogramming and Therapeutic Resistance in Cancer. Int J Mol Sci 2022; 23:ijms232314808. [PMID: 36499136 PMCID: PMC9738059 DOI: 10.3390/ijms232314808] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/23/2022] [Accepted: 11/24/2022] [Indexed: 12/02/2022] Open
Abstract
Metabolic alterations that support the supply of biosynthetic molecules necessary for rapid and sustained proliferation are characteristic of cancer. Some cancer cells rely on glutamine to maintain their energy requirements for growth. Glutamine is an important metabolite in cells because it not only links to the tricarboxylic acid cycle by producing α-ketoglutarate by glutaminase and glutamate dehydrogenase but also supplies other non-essential amino acids, fatty acids, and components of nucleotide synthesis. Altered glutamine metabolism is associated with cancer cell survival, proliferation, metastasis, and aggression. Furthermore, altered glutamine metabolism is known to be involved in therapeutic resistance. In recent studies, lncRNAs were shown to act on amino acid transporters and glutamine-metabolic enzymes, resulting in the regulation of glutamine metabolism. The lncRNAs involved in the expression of the transporters include the abhydrolase domain containing 11 antisense RNA 1, LINC00857, plasmacytoma variant translocation 1, Myc-induced long non-coding RNA, and opa interacting protein 5 antisense RNA 1, all of which play oncogenic roles. When it comes to the regulation of glutamine-metabolic enzymes, several lncRNAs, including nuclear paraspeckle assembly transcript 1, XLOC_006390, urothelial cancer associated 1, and thymopoietin antisense RNA 1, show oncogenic activities, and others such as antisense lncRNA of glutaminase, lincRNA-p21, and ataxin 8 opposite strand serve as tumor suppressors. In addition, glutamine-dependent cancer cells with lncRNA dysregulation promote cell survival, proliferation, and metastasis by increasing chemo- and radio-resistance. Therefore, understanding the roles of lncRNAs in glutamine metabolism will be helpful for the establishment of therapeutic strategies for glutamine-dependent cancer patients.
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Affiliation(s)
- Jungwook Roh
- Department of Science Education, Korea National University of Education, Cheongju-si 28173, Chungbuk, Republic of Korea
| | - Mijung Im
- Department of Science Education, Korea National University of Education, Cheongju-si 28173, Chungbuk, Republic of Korea
| | - Yeonsoo Chae
- Department of Science Education, Korea National University of Education, Cheongju-si 28173, Chungbuk, Republic of Korea
| | - JiHoon Kang
- Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Wanyeon Kim
- Department of Science Education, Korea National University of Education, Cheongju-si 28173, Chungbuk, Republic of Korea
- Department of Biology Education, Korea National University of Education, Cheongju-si 28173, Chungbuk, Republic of Korea
- Correspondence: ; Tel.: +82-43-230-3750
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Liu K, Du Y, Li H, Lin X. Identification of super-enhancer-associated transcription factors regulating glucose metabolism in poorly differentiated thyroid carcinoma. Genet Mol Biol 2022; 45:e20210370. [PMID: 36121916 PMCID: PMC9495016 DOI: 10.1590/1678-4685-gmb-2021-0370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 06/05/2022] [Indexed: 12/24/2022] Open
Abstract
This study aimed to uncover transcription factors that regulate super-enhancers involved in glucose metabolism reprogramming in poorly differentiated thyroid carcinoma (PDTC). TCA cycle and pyruvate metabolism were significantly enriched in PDTC. Differentially expressed genes in PDTC vs. normal control tissues were located in key steps in TCA cycle and pyruvate metabolism. A total of 23 upregulated genes localized in TCA cycle and pyruvate metabolism were identified as super-enhancer-controlled genes. Transcription factor analysis of these 23 super-enhancer-controlled genes related to glucose metabolism was performed, and 20 transcription factors were obtained, of which KLF12, ZNF281 and RELA had a significant prognostic impact. Regulatory network of KLF12, ZNF281 and RELA controlled the expression of these four prognostic target genes (LDHA, ACLY, ME2 and IDH2). In vitro validation showed that silencing of KLF12, ZNF281 and RELA suppressed proliferation, glucose uptake, lactate production and ATP level, but increased ADP/ATP ratio in PDTC cells. In conclusion, KLF12, ZNF281 and RELA were identified as the key transcription factors that regulate super-enhancer-controlled genes related to glucose metabolism in PDTC. Our findings contribute to a deeper understanding of the regulatory mechanisms associated with glucose metabolism in PDTC, and advance the theoretical development of PDTC-targeted therapies.
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Affiliation(s)
- Kun Liu
- Tianjin Hospital, Endocrinology Department, Tianjin, P. R. China
| | - Yongrui Du
- 80th Group Military Hospital, Chinese Peoples Liberation Army, Endocrinology Department, Weifang, Shandong, P. R. China
| | - Hui Li
- XingTai Medical College, Basic Experiment Center, Xingtai, Hebei, P. R. China
| | - Xuexia Lin
- XingTai Medical College, Basic Experiment Center, Xingtai, Hebei, P. R. China
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Wang M, Liu X, Chen T, Cheng X, Xiao H, Meng X, Jiang Y. Inhibition and potential treatment of colorectal cancer by natural compounds via various signaling pathways. Front Oncol 2022; 12:956793. [PMID: 36158694 PMCID: PMC9496650 DOI: 10.3389/fonc.2022.956793] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/15/2022] [Indexed: 11/13/2022] Open
Abstract
Colorectal cancer (CRC) is a common type of malignant digestive tract tumor with a high incidence rate worldwide. Currently, the clinical treatment of CRC predominantly include surgical resection, postoperative chemotherapy, and radiotherapy. However, these treatments contain severe limitations such as drug side effects, the risk of recurrence and drug resistance. Some natural compounds found in plants, fungi, marine animals, and bacteria have been shown to inhibit the occurrence and development of CRC. Although the explicit molecular mechanisms underlying the therapeutic effects of these compounds on CRC are not clear, classical signaling transduction pathways such as NF-kB and Wnt/β-catenin are extensively regulated. In this review, we have summarized the specific mechanisms regulating the inhibition and development of CRC by various types of natural compounds through nine signaling pathways, and explored the potential therapeutic values of these natural compounds in the clinical treatment of CRC.
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Affiliation(s)
- Mingchuan Wang
- Department of Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xianjun Liu
- College of Food Engineering, Jilin Engineering Normal University, Changchun, China
| | - Tong Chen
- Department of Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xianbin Cheng
- Department of Thyroid Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Huijie Xiao
- Department of Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xianglong Meng
- Department of Burns Surgery, The First Hospital of Jilin University, Changchun, China
| | - Yang Jiang
- Department of Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun, China
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Luo Z, Chen R, Hu S, Huang X, Huang Z. PVT1 promotes resistance to 5‑FU in colon cancer via the miR‑486‑5p/CDK4 axis. Oncol Lett 2022; 24:280. [PMID: 35814832 PMCID: PMC9260730 DOI: 10.3892/ol.2022.13400] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 05/12/2022] [Indexed: 11/21/2022] Open
Abstract
Drug resistance in tumors is a major issue, limiting the curative efficacy of currently available cancer chemotherapeutics. 5-Fluorouracil (5-FU) is a commonly applied therapeutic drug in colon cancer patient regimens; however, the majority of patients develop resistance to 5-FU in the later stages of the disease, rendering this chemotherapy ineffective. Drug resistance is the main factor underlying the poor prognosis of patients with colon cancer. In recent years, a number of studies have confirmed that long non-coding (lnc)RNAs may play vital roles in tumor resistance. In the present study, the Gene Expression Omnibus (GEO) and lncRNADisease2 databases were screened for colon cancer-associated expression patterns of lncRNA plasmacytoma variant translocation 1 (PVT1). Subsequently, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect changes in PVT1 expression in resistant cell lines, and a Cell Counting Kit-8 (CCK-8) assay kit was used to assess the effects of PVT1 knockdown on the half maximal inhibitory concentrations of parental and 5-FU-resistant HCT116 cells. Subsequently, CCK-8, clone formation, and flow cytometric assays were performed to investigate the effects of PVT1 knockdown on the sensitivity of HCT116-5FU-resistant cells to 5-FU. Dual-luciferase assay, RNA pull-down and RNA immunoprecipitation assays verified the interactive regulation of PVT1, miR-486-5p and cyclin dependent kinase 4 (CDK4). PVT1 was highly expressed in HCT116-5FU-resistant cells, as compared to its expression in HCT116 parental cells. PVT1 knockdown significantly reduced the resistance of HCT116-5FU-resistant cells to 5-FU. In addition, PVT1 upregulated CDK4 expression by adsorbing miR-486-5p; however, CDK4 overexpression restored the effects of miR-486-5p inhibition on HCT116-5-FU-resistant cells. Additionally, PVT1 knockdown partially rescued CDK4 overexpression in HCT116-5-FU-resistant cells. On the whole, the findings of the present study suggest that PVT1 promotes the resistance of colon cancer cells to 5-FU by regulating the miR-486-5p/CDK4 axis. Therefore, PVT1 may prove to be a potential target for counteracting resistance to 5-FU in colon cancer therapy.
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Affiliation(s)
- Zhuhe Luo
- Department of Pharmacy, Huizhou Central People's Hospital, Huizhou, Guangdong 516001, P.R. China
| | - Ruijun Chen
- Department of Pharmacy, Huizhou Central People's Hospital, Huizhou, Guangdong 516001, P.R. China
| | - Shen Hu
- Department of Gastrointestinal Surgery, Huizhou Central People's Hospital, Huizhou, Guangdong 516001, P.R. China
| | - Xibin Huang
- Guangzhou Genetech Gene Technology Co., Ltd., Huizhou, Guangdong 516001, P.R. China
| | - Zhenyi Huang
- Department of Pharmacy, Huizhou First People's Hospital, Huizhou, Guangdong 516001, P.R. China
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29
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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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30
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Wang N, Fan H, Fu S, Li S, Zhou B, Jin Q, You Z. Long noncoding RNA UCA1 promotes carboplatin resistance in retinoblastoma cells by acting as a ceRNA of miR-206. Am J Cancer Res 2022; 12:2160-2172. [PMID: 35693085 PMCID: PMC9185611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 04/19/2022] [Indexed: 06/15/2023] Open
Abstract
Chemoresistance has become a major obstacle to effective retinoblastoma treatment. The urothelial cancer-associated gene 1 (UCA1) is commonly considered an oncogene in certain types of cancer and is related to drug resistance. Nonetheless, the molecular mechanism and effect of UCA1 in carboplatin resistance in retinoblastoma are unclear. In this study, UCA1 expression was determined by sequential screening and lncRNA profile analysis, which is highly abundant in carboplatin-resistant retinoblastoma cells. Functional analyses revealed that UCA1 promoted carboplatin resistance by promoting c-Met and AXL expression. Mechanistic studies revealed that UCA1 facilitated c-Met and AXL expression as a ceRNA of miR-206. Importantly, retinoblastoma nude mouse model experiments revealed that targeting UCA1 or c-Met and AXL can restore drug sensitivity in carboplatin-resistant retinoblastoma. Collectively, we found that UCA1 is a mediator of carboplatin resistance in retinoblastoma cells. It competes with others as the endogenous RNA of miR-206, thus upregulating its targets, c-MET and AXL expression.
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Affiliation(s)
- Nanye Wang
- Department of Ophthalmology, The Second Affiliated Hospital of Nanchang UniversityNanchang 330006, Jiangxi, China
| | - Huimin Fan
- Department of Ophthalmology, The Second Affiliated Hospital of Nanchang UniversityNanchang 330006, Jiangxi, China
| | - Shuhua Fu
- Department of Ophthalmology, The Second Affiliated Hospital of Nanchang UniversityNanchang 330006, Jiangxi, China
| | - Shaojun Li
- Department of Ophthalmology, The Second Affiliated Hospital of Nanchang UniversityNanchang 330006, Jiangxi, China
| | - Bin Zhou
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang UniversityNanchang 330006, Jiangxi, China
| | - Qifang Jin
- Department of Ophthalmology, The Second Affiliated Hospital of Nanchang UniversityNanchang 330006, Jiangxi, China
| | - Zhipeng You
- Department of Ophthalmology, The Second Affiliated Hospital of Nanchang UniversityNanchang 330006, Jiangxi, China
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Chen F, Zhang X, Chen Y, Chai Y, Jiang X, Li H. Construction of lncRNA-miRNA-mRNA network based on ceRNA mechanism reveals the function of lncRNA in the pathogenesis of gout. J Clin Lab Anal 2022; 36:e24451. [PMID: 35524416 PMCID: PMC9169187 DOI: 10.1002/jcla.24451] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/18/2022] [Accepted: 04/12/2022] [Indexed: 11/23/2022] Open
Abstract
Objective To identify differentially expressed lncRNA, miRNA, and mRNA during the pathogenesis of gout, explore the ceRNA network regulatory mechanism of gout, and seek potential therapeutic targets. Method First, gout‐related chips were retrieved by GEO database. Then, the analysis of differentially expressed lncRNAs and mRNAs was conducted by R language and other software. Besides, miRNA and its regulated mRNA were predicted based on public databases, the intersection of differentially expressed mRNA and predicated mRNA was taken, and the lncRNA‐miRNA‐mRNA regulatory relationships were obtained to construct the ceRNA regulatory network. Subsequently, hub genes were screened by the STRING database and Cytoscape software. Then the DAVID database was used to illustrate the gene functions and related pathways of hub genes and to mine key ceRNA networks. Results Three hundred and eighty‐eight lncRNAs and 758 mRNAs were identified with significant differential expression in gout patient, which regulates hub genes in the ceRNA network, such as JUN, FOS, PTGS2, NR4A2, and TNFAIP3. In the ceRNA network, lncRNA competes with mRNA for miRNA, thus affecting the IL‐17 signaling pathway, TNF signaling pathway, Oxytocin signaling pathway, and NF‐κB signaling pathway through regulating the cell's response to chemical stress. The research indicates that five miRNAs (miR‐429, miR‐137, miR‐139‐5p, miR‐217, miR‐23b‐3p) and five lncRNAs (SNHG1, FAM182A, SPAG5‐AS1, HNF1A‐AS1, UCA1) play an important role in the formation and development of gout. Conclusion The interaction in the ceRNA network can affect the formation and development of gout by regulating the body's inflammatory response as well as proliferation, differentiation, and apoptosis of chondrocytes and osteoclasts. The identification of potential therapeutic targets and signaling pathways through ceRNA network can provide a reference for further research on the pathogenesis of gout.
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Affiliation(s)
- Feng Chen
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Xiaoyun Zhang
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Yueping Chen
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Yuan Chai
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Xiao Jiang
- The Second Hospital of Dalian Medical University, DaLian, China
| | - Huanan Li
- Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China
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Wo L, Zhang B, You X, Hu Y, Gu Z, Zhang M, Wang Q, Lv Z, Zhao H. Up-regulation of LncRNA UCA1 by TGF-β promotes doxorubicin resistance in breast cancer cells. Immunopharmacol Immunotoxicol 2022; 44:492-499. [PMID: 35332839 DOI: 10.1080/08923973.2022.2054428] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Doxorubicin (DOX) resistance remains a major challenge for adriamycin-based treatment of breast cancer (BC). Transforming growth factor β (TGF-β) has been reported to contribute to drug resistance. Although the role of long noncoding RNAs (LncRNAs) in cancer progression has been widely studied, its effect on TGF-β-induced resistance remains limited. This study aimed to investigate the role of LncRNA on the regulation of TGF-β-induced drug resistance. METHODS Cell counting kit-8 (CCK-8) and an EdU assay were used to evaluate cell viability and proliferation. The level of LncRNA mRNA expression in BC tissues and cells was examined by quantitative real-time PCR. Changes in epithelial-mesenchymal transition (EMT) and cell apoptosis were quantified by Western blot and immunofluorescence. RESULTS TGF-β induced EMT and promoted DOX resistance. LncRNA urothelial carcinoma-associated 1(lncRNA UCA1) associated with TGF-β was upregulated in BC cells and tissues. LncRNA UCA1 silencing enhanced sensitivity to DOX decreased cellular proliferation and increased apoptosis in BC cells. The effect of TGF-β on EMT and DOX resistance disappeared following a lncRNA UCA1 knockdown. CONCLUSIONS These findings suggest that lncRNA-UCA1, a mediator of TGF-β signaling, could predispose BC patients to EMT and DOX resistance.
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Affiliation(s)
- Like Wo
- Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
| | - Bei Zhang
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
| | - Xiongbin You
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
| | - Yuanyuan Hu
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
| | - Zhenqi Gu
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
| | - Mengning Zhang
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
| | - Qi Wang
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
| | - Zhengyi Lv
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
| | - Hong Zhao
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
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Zuo J, Zhang Z, Li M, Yang Y, Zheng B, Wang P, Huang C, Zhou S. The crosstalk between reactive oxygen species and noncoding RNAs: from cancer code to drug role. Mol Cancer 2022; 21:30. [PMID: 35081965 PMCID: PMC8790843 DOI: 10.1186/s12943-021-01488-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 12/26/2021] [Indexed: 02/08/2023] Open
Abstract
Oxidative stress (OS), characterized by the excessive accumulation of reactive oxygen species (ROS), is an emerging hallmark of cancer. Tumorigenesis and development driven by ROS require an aberrant redox homeostasis, that activates onco-signaling and avoids ROS-induced programmed death by orchestrating antioxidant systems. These processes are revealed to closely associate with noncoding RNAs (ncRNAs). On the basis of the available evidence, ncRNAs have been widely identified as multifarious modulators with the involvement of several key redox sensing pathways, such as NF-κB and Nrf2 signaling, therefore potentially becoming effective targets for cancer therapy. Furthermore, the vast majority of ncRNAs with property of easy detected in fluid samples (e.g., blood and urine) facilitate clinicians to monitor redox homeostasis, indicating a novel method for cancer diagnosis. Herein, focusing on carcinoma initiation, metastasis and chemoradiotherapy resistance, we aimed to discuss the ncRNAs-ROS network involved in cancer progression, and the potential clinical application as biomarkers and therapeutic targets.
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Affiliation(s)
- Jing Zuo
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China
| | - Zhe Zhang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China
| | - Maomao Li
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China
| | - Yun Yang
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China
| | - Bohao Zheng
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China
| | - Ping Wang
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China.
| | - Canhua Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, People's Republic of China.
| | - Shengtao Zhou
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China.
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Lei GL, Li Z, Li YY, Hong ZX, Wang S, Bai ZF, Sun F, Yan J, Yu LX, Yang PH, Yang ZY. Long noncoding RNA FAM66C promotes tumor progression and glycolysis in intrahepatic cholangiocarcinoma by regulating hsa-miR-23b-3p/KCND2 axis. ENVIRONMENTAL TOXICOLOGY 2021; 36:2322-2332. [PMID: 34418280 DOI: 10.1002/tox.23346] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 08/04/2021] [Accepted: 08/04/2021] [Indexed: 06/13/2023]
Abstract
Long noncoding RNAs (lncRNAs) are known to be the important regulators in cancer progression. However, the role of lncRNA FAM66C (FAM66C) is yet to be investigated in intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate the effects and related mechanisms of FAM66C in ICC. Human ICC tissues and cell lines were collected. The expression levels of FAM66C, hsa-miR-23b-3p (miR-23b-3p), and KCND2 were detected by qRT-RCR. The transfection experiments were employed to measure the effect of FAM66C on cell viabilities, migration, and invasion in ICC cells by CCK-8, transwell assays. Glycolysis was investigated by glucose consumption, lactate production and ATP levels. The dual-luciferase reporter and RNA pull down assays were conducted as a means of confirming the interactions between FAM66C, miR-23b-3p, and KCND2. Furthermore, the levels of the EMT-associated proteins (KCND2, GLUT1, PKM2, and LDHA) in ICC cells were detected by western blot. FAM66C was increased in ICC tissues and cells, increased cell viability, glycolysis, migration and invasion, and decreased apoptosis were shown in FAM66C overexpressing cells. Mechanistic analyses revealed that FAM66C regulated the downstream target gene KCND2 by sponging miR-23b-3p. FAM66C effect on ICC was further validated in murine xenograft assays. FAM66C knockdown cells gave rise to tumors that were smaller in size, consistent with the role of FAM66C as a promoter of in vivo tumor growth. These data revealed that FAM66C was able to drive ICC tumor progression and glycolytic activity via the miR-23b-3p/KCND2 axis, indicating FAM66C may be a viable target for treating ICC.
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Affiliation(s)
- Guang-Lin Lei
- Medical School of Chinese PLA, Beijing, China
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhi Li
- Medical School of Chinese PLA, Beijing, China
- Senior Department of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yuan-Yuan Li
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhi-Xian Hong
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Sen Wang
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhi-Fang Bai
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Fang Sun
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jin Yan
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ling-Xiang Yu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Peng-Hui Yang
- Medical School of Chinese PLA, Beijing, China
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhan-Yu Yang
- Medical School of Chinese PLA, Beijing, China
- Senior Department of Hepato-Pancreato-Biliary Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
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35
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Li P, Wen J, Ren X, Zhou Y, Xue Y, Yan Z, Li S, Tian H, Tang XG, Zhang GJ. MicroRNA-23b-3p targets non-SMC condensing I complex subunit G to promote proliferation and inhibit apoptosis of colorectal cancer cells via regulation of the PI3K/AKT signaling pathway. Oncol Lett 2021; 22:812. [PMID: 34671426 PMCID: PMC8503806 DOI: 10.3892/ol.2021.13073] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/31/2021] [Indexed: 01/01/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common types of malignancy worldwide and has a poor prognosis. Non-SMC condensing I complex subunit G (NCAPG) has been reported to be upregulated in numerous types of malignant tumor. However, to the best of our knowledge, its clinicopathological and biological significance in CRC remain to be elucidated. The results of the present study revealed that NCAPG expression levels were upregulated in human CRC tissues and cell lines. The upregulated expression of NCAPG was positively associated with patient clinicopathological characteristics, such as differentiation and tumor size, and independently associated with poor survival. Consistent with the clinical observations, NCAPG was discovered to promote the proliferation and inhibit the apoptosis of CRC cells. Moreover, NCAPG-knockdown inhibited CRC cell proliferation by regulating the PI3K/AKT signaling pathway. Furthermore, NCAPG was identified as a potential target of microRNA (miR)-23b-3p, which was subsequently demonstrated to negatively regulate NCAPG expression. In conclusion, the findings of the current study indicated that the miR-23b-3p/NCAPG/PI3K/AKT signaling axis may play an important role in CRC carcinogenesis, and the status of the molecule may represent a promising prognostic marker for the disease.
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Affiliation(s)
- Peidong Li
- The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.,Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Jing Wen
- The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.,Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Xiru Ren
- Nanchong Inspection Institute for Food and Drugs, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Yu Zhou
- The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.,Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Yuan Xue
- The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.,Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Zaihua Yan
- The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.,Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Shengjie Li
- The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.,Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Hongpeng Tian
- The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Xue-Gui Tang
- Anorectal Department of Integrated Traditional Chinese and Western Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Guang-Jun Zhang
- The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.,Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
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Luo M, Yang X, Chen HN, Nice EC, Huang C. Drug resistance in colorectal cancer: An epigenetic overview. Biochim Biophys Acta Rev Cancer 2021; 1876:188623. [PMID: 34481016 DOI: 10.1016/j.bbcan.2021.188623] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 08/29/2021] [Accepted: 08/30/2021] [Indexed: 02/08/2023]
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Despite significant progress that has been made in therapies against CRC over the past decades, drug resistance is still a major limitation in CRC treatment. Numerous investigations have unequivocally shown that epigenetic regulation plays an important role in CRC drug resistance because of the high rate of epigenetic alterations in multiple genes during cancer development or drug treatment. Furthermore, the reversibility of epigenetic alterations provides novel therapeutic strategies to overcome drug resistance using small molecules, which can target non-coding RNAs or reverse histone modification and DNA methylation. In this review, we discuss epigenetic regulation in CRC drug resistance and the possible role of preventing or reversing CRC drug resistance using epigenetic therapy in CRC treatment.
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Affiliation(s)
- Maochao Luo
- The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang 315020, China; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
| | - Xingyue Yang
- The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang 315020, China; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
| | - Hai-Ning Chen
- Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Edouard C Nice
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
| | - Canhua Huang
- The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang 315020, China; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
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Chen L, He M, Zhang M, Sun Q, Zeng S, Zhao H, Yang H, Liu M, Ren S, Meng X, Xu H. The Role of non-coding RNAs in colorectal cancer, with a focus on its autophagy. Pharmacol Ther 2021; 226:107868. [PMID: 33901505 DOI: 10.1016/j.pharmthera.2021.107868] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 04/16/2021] [Accepted: 04/20/2021] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is one of malignant afflictions burdening people worldwide, mainly caused by shortages of effective medical intervention and poorly mechanistic understanding of the pathogenesis of CRC. Non-coding RNAs (ncRNAs) are a type of heterogeneous transcripts without the capability of coding protein, but have the potency of regulating protein-coding gene expression. Autophagy is an evolutionarily conserved catabolic process in which cytoplasmic contents are delivered to cellular lysosomes for degradation, resulting in the turnover of cellular components and producing energy for cell functions. A growing body of evidence reveals that ncRNAs, autophagy, and the crosstalks of ncRNAs and autophagy play intricate roles in the initiation, progression, metastasis, recurrence and therapeutic resistance of CRC, which confer ncRNAs and autophagy to serve as clinical biomarkers and therapeutic targets for CRC. In this review, we sought to delineate the complicated roles of ncRNAs, mainly including miRNAs, lncRNAs and circRNAs, in the pathogenesis of CRC, particularly focus on the regulatory role of ncRNAs in CRC-related autophagy, attempting to shed light on the complex pathological mechanisms, involving ncRNAs and autophagy, responsible for CRC tumorigenesis and development, so as to underpin the ncRNAs- and autophagy-based therapeutic strategies for CRC in clinical setting.
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Affiliation(s)
- Li Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Man He
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Meng Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Qiang Sun
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Sha Zeng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Hui Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Han Yang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Maolun Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Shan Ren
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xianli Meng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Haibo Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacology, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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Ramli S, Sim MS, Guad RM, Gopinath SCB, Subramaniyan V, Fuloria S, Fuloria NK, Choy KW, Rana S, Wu YS. Long Noncoding RNA UCA1 in Gastrointestinal Cancers: Molecular Regulatory Roles and Patterns, Mechanisms, and Interactions. JOURNAL OF ONCOLOGY 2021; 2021:5519720. [PMID: 33936199 PMCID: PMC8055404 DOI: 10.1155/2021/5519720] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/15/2021] [Accepted: 03/26/2021] [Indexed: 02/08/2023]
Abstract
The rising trend of gastrointestinal (GI) cancer has become a global burden due to its aggressive nature and poor prognosis. Long noncoding RNAs (lncRNAs) have recently been reported to be overexpressed in different GI cancers and may contribute to cancer progression and chemoresistance. They are featured with more than 200 nucleotides, commonly polyadenylated, and lacking an open reading frame. LncRNAs, particularly urothelial carcinoma-associated 1 (UCA1), are oncogenes involved in regulating cancer progression, such as cell proliferation, invasion, migration, and chemoresistance, particularly in GI cancer. This review was aimed to present an updated focus on the molecular regulatory roles and patterns of lncRNA UCA1 in progression and chemoresistance of different GI cancers, as well as deciphering the underlying mechanisms and its interactions with key molecules involved, together with a brief presentation on its diagnostic and prognostic values. The regulatory roles of lncRNA UCA1 are implicated in esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, and colorectal cancer, where they shared similar molecular mechanisms in regulating cancer phenotypes and chemoresistance. Comparatively, gastric cancer is the most intensively studied type in GI cancer. LncRNA UCA1 is implicated in biological roles of different GI cancers via interactions with various molecules, particularly microRNAs, and signaling pathways. In conclusion, lncRNA UCA1 is a potential molecular target for GI cancer, which may lead to the development of a novel chemotherapeutic agent. Hence, it also acts as a potential diagnostic and prognostic marker for GI cancer patients.
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Affiliation(s)
- Suaidah Ramli
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Maw Shin Sim
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Rhanye M. Guad
- Department of Biomedical Science and Therapeutics, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
| | - Subash C. B Gopinath
- School of Bioprocess Engineering, Universiti Malaysia Perlis, Arau 02600, Perlis, Malaysia
- Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, Kangar 01000, Perlis, Malaysia
| | - Vetriselvan Subramaniyan
- Department of Pharmacology, School of Medicine, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom, Selangor 42610, Malaysia
| | - Shivkanya Fuloria
- Faculty of Pharmacy, AIMST University, Bedong, Kedah 08100, Malaysia
| | - Neeraj K. Fuloria
- Faculty of Pharmacy, AIMST University, Bedong, Kedah 08100, Malaysia
| | - Ker Woon Choy
- Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Shah Alam, Sungai Buloh 47000, Selangor, Malaysia
| | - Sohel Rana
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore-7400, Bangladesh
| | - Yuan Seng Wu
- Department of Biochemistry, School of Medicine, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom, Selangor 42610, Malaysia
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Micallef I, Baron B. The Mechanistic Roles of ncRNAs in Promoting and Supporting Chemoresistance of Colorectal Cancer. Noncoding RNA 2021; 7:24. [PMID: 33807355 PMCID: PMC8103280 DOI: 10.3390/ncrna7020024] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/03/2021] [Accepted: 03/29/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal Cancer (CRC) is one of the most common gastrointestinal malignancies which has quite a high mortality rate. Despite the advances made in CRC treatment, effective therapy is still quite challenging, particularly due to resistance arising throughout the treatment regimen. Several studies have been carried out to identify CRC chemoresistance mechanisms, with research showing different signalling pathways, certain ATP binding cassette (ABC) transporters and epithelial mesenchymal transition (EMT), among others to be responsible for the failure of CRC chemotherapies. In the last decade, it has become increasingly evident that certain non-coding RNA (ncRNA) families are involved in chemoresistance. Research investigations have demonstrated that dysregulation of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) contribute towards promoting resistance in CRC via different mechanisms. Considering the currently available data on this phenomenon, a better understanding of how these ncRNAs participate in chemoresistance can lead to suitable solutions to overcome this problem in CRC. This review will first focus on discussing the different mechanisms of CRC resistance identified so far. The focus will then shift onto the roles of miRNAs, lncRNAs and circRNAs in promoting 5-fluorouracil (5-FU), oxaliplatin (OXA), cisplatin and doxorubicin (DOX) resistance in CRC, specifically using ncRNAs which have been recently identified and validated under in vivo or in vitro conditions.
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Affiliation(s)
| | - Byron Baron
- Centre for Molecular Medicine and Biobanking, University of Malta, MSD2080 Msida, Malta;
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40
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Yang D, Wang Y, Zheng Y, Dai F, Liu S, Yuan M, Deng Z, Bao A, Cheng Y. Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K/AKT signaling pathway. J Ovarian Res 2021; 14:48. [PMID: 33743811 PMCID: PMC7980617 DOI: 10.1186/s13048-021-00792-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 03/01/2021] [Indexed: 02/07/2023] Open
Abstract
Background Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-aged women worldwide, however, the mechanisms and progression of PCOS still unclear due to its heterogeneous nature. Using the human granulosa-like tumor cell line (KGN) and PCOS mice model, we explored the function of lncRNA UCA1 in the pathological progression of PCOS. Results CCK8 assay and Flow cytometry were used to do the cell cycle, apoptosis and proliferation analysis, the results showed that UCA1 knockdown in KGN cells inhibited cell proliferation by blocking cell cycle progression and promoted cell apoptosis. In the in vivo experiment, the ovary of PCOS mice was injected with lentivirus carrying sh-UCA1, the results showed that knockdown of lncRNA UCA1 attenuated the ovary structural damage, increased the number of granular cells, inhibited serum insulin and testosterone release, and reduced the pro-inflammatory cytokine production. Western blot also revealed that UCA1 knockdown in PCOS mice repressed AKT activation, inhibitor experiment demonstrated that suppression of AKT signaling pathway, inhibited the cell proliferation and promoted apoptosis. Conclusions Our study revealed that, in vitro, UCA1 knockdown influenced the apoptosis and proliferation of KGN cells, in vivo, silencing of UCA1 regulated the ovary structural damage, serum insulin release, pro-inflammatory production, and AKT signaling pathway activation, suggesting lncRNA UCA1 plays an important role in the pathological progression of PCOS.
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Affiliation(s)
- Dongyong Yang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yanqing Wang
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yajing Zheng
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Fangfang Dai
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shiyi Liu
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Mengqin Yuan
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhimin Deng
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Anyu Bao
- Department of Clinical Laboratoy, Renmin Hospital of Wuhan University, Wuhan, China.
| | - Yanxiang Cheng
- Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.
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Parisi A, Porzio G, Pulcini F, Cannita K, Ficorella C, Mattei V, Delle Monache S. What Is Known about Theragnostic Strategies in Colorectal Cancer. Biomedicines 2021; 9:biomedicines9020140. [PMID: 33535557 PMCID: PMC7912746 DOI: 10.3390/biomedicines9020140] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 02/08/2023] Open
Abstract
Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms. On the other hand, preclinical and clinical evidence demonstrated the role of gut microbiota dysbiosis in promoting inflammatory responses and cancer initiation. Altered gut microbiota is associated with resistance to chemo drugs and immune checkpoint inhibitors, whereas the use of microbe-targeted therapies including antibiotics, pre-probiotics, and fecal microbiota transplantation can restore response to anticancer drugs, promote immune response, and therefore support current treatment strategies in CRC. In this review, we aim to summarize preclinical and clinical evidence for the utilization of liquid biopsy and gut microbiota in CRC.
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Affiliation(s)
- Alessandro Parisi
- Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy;
- Medical Oncology Unit, St. Salvatore Hospital, 67100 L’Aquila, Italy; (G.P.); (K.C.); (C.F.)
| | - Giampiero Porzio
- Medical Oncology Unit, St. Salvatore Hospital, 67100 L’Aquila, Italy; (G.P.); (K.C.); (C.F.)
- Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy;
| | - Fanny Pulcini
- Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy;
| | - Katia Cannita
- Medical Oncology Unit, St. Salvatore Hospital, 67100 L’Aquila, Italy; (G.P.); (K.C.); (C.F.)
- Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy;
| | - Corrado Ficorella
- Medical Oncology Unit, St. Salvatore Hospital, 67100 L’Aquila, Italy; (G.P.); (K.C.); (C.F.)
- Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy;
| | - Vincenzo Mattei
- Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, via Angelo Maria Ricci 35A, 02100 Rieti, Italy;
| | - Simona Delle Monache
- Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy;
- Correspondence: ; Tel.: +39-086-243-3569
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Zhao YJ, Chen YE, Zhang HJ, Gu X. LncRNA UCA1 remits LPS-engendered inflammatory damage through deactivation of miR-499b-5p/TLR4 axis. IUBMB Life 2020; 73:463-473. [PMID: 33368965 DOI: 10.1002/iub.2443] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 12/17/2020] [Indexed: 12/17/2022]
Abstract
Neonatal pneumonia is a high neonatal mortality disease. The current research was designed to elucidate the modulatory function and feasible molecular mechanism of UCA1 in LPS-induced injury in pneumonia. Herein, LPS was applied to induce WI-38 cell inflammatory damage. We displayed that UCA1 was elevated in LPS-injured WI-38 cells. In the functional aspect, intervention of UCA1 evidently aggrandized cell viability in LPS-triggered WI-38 cells. In the meanwhile, elimination of UCA1 distinctly assuaged cell apoptosis concomitant with declined levels of proapoptotic proteins Bax and C-caspase-3, and ascended the expression of antiapoptotic protein Bcl-2. Subsequently, disruption of UCA1 manifestly restrained inflammatory damage as characterized by declination of multiple pro-inflammatory factors IL-1β, IL-6, and TNF-α in WI-38 cells under LPS circumstance. More importantly, we predicted and verified that UCA1 functioned as a ceRNA by efficaciously binding to miR-499b-5p thereby inversely adjusting miR-499b-5p expression. Interesting, TLR4 was identified as direct target of miR-499b-5p, and positively regulated by UCA1 through sponging miR-499b-5p. Mechanistically, absence of miR-499b-5p or restoration of TLR4 impeded the beneficial effects of UCA1 ablation on LPS-stimulated apoptosis and inflammatory response. Collectively, these observations illuminated that UCA1 inhibition protected WI-38 cells against LPS-managed inflammatory injury and apoptosis process via miR-499b-5p/TLR4 crosstalk, which ultimately influencing the development of pneumonia.
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Affiliation(s)
- Yan-Jun Zhao
- Department of Respiratory and Critical Care Medicine, Xi'an Chest Hospital, Xi'an TB and Thoracic Tumor Hospital, Xi'an, PR China
| | - Yue-E Chen
- Department of Respiratory and Critical Care Medicine, Xi'an Chest Hospital, Xi'an TB and Thoracic Tumor Hospital, Xi'an, PR China
| | - Hong-Jun Zhang
- Department of Respiratory and Critical Care Medicine, Xi'an Chest Hospital, Xi'an TB and Thoracic Tumor Hospital, Xi'an, PR China
| | - Xing Gu
- Department of Respiratory and Critical Care Medicine, Xi'an Chest Hospital, Xi'an TB and Thoracic Tumor Hospital, Xi'an, PR China
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