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Saadh MJ, Ehymayed HM, Alazzawi TS, Fahdil AA, Athab ZH, Yarmukhamedov B, Al-Anbari HHA, Shallal MM, Alsaikhan F, Farhood B. Role of circRNAs in regulating cell death in cancer: a comprehensive review. Cell Biochem Biophys 2025; 83:109-133. [PMID: 39243349 DOI: 10.1007/s12013-024-01492-6] [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] [Accepted: 08/21/2024] [Indexed: 09/09/2024]
Abstract
Despite multiple diagnostic and therapeutic advances, including surgery, radiation therapy, and chemotherapy, cancer preserved its spot as a global health concern. Prompt cancer diagnosis, treatment, and prognosis depend on the discovery of new biomarkers and therapeutic strategies. Circular RNAs (circRNAs) are considered as a stable, conserved, abundant, and varied group of RNA molecules that perform multiple roles such as gene regulation. There is evidence that circRNAs interact with RNA-binding proteins, especially capturing miRNAs. An extensive amount of research has presented the substantial contribution of circRNAs in various types of cancer. To fully understand the linkage between circRNAs and cancer growth as a consequence of various cell death processes, including autophagy, ferroptosis, and apoptosis, more research is necessary. The expression of circRNAs could be controlled to limit the occurrence and growth of cancer, providing a more encouraging method of cancer treatment. Consequently, it is critical to understand how circRNAs affect various forms of cancer cell death and evaluate whether circRNAs could be used as targets to induce tumor death and increase the efficacy of chemotherapy. The current study aims to review and comprehend the effects that circular RNAs exert on cell apoptosis, autophagy, and ferroptosis in cancer to investigate potential cancer treatment targets.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | | | - Tuqa S Alazzawi
- College of dentist, National University of Science and Technology, Dhi Qar, Iraq
| | - Ali A Fahdil
- Medical technical college, Al-Farahidi University, Baghdad, Iraq
| | - Zainab H Athab
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
| | - Bekhzod Yarmukhamedov
- Department of Surgical Dentistry and Dental Implantology, Tashkent State Dental Institute, Tashkent, Uzbekistan
- Department of Scientific affairs, Samarkand State Medical University, Samarkand, Uzbekistan
| | | | | | - Fahad Alsaikhan
- College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia.
- School of Pharmacy, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia.
| | - Bagher Farhood
- Department of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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Olbromski M, Mrozowska M, Smolarz B, Romanowicz H, Rusak A, Piotrowska A. ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B. Sci Rep 2024; 14:26935. [PMID: 39505971 PMCID: PMC11541733 DOI: 10.1038/s41598-024-78432-0] [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: 06/28/2024] [Accepted: 10/30/2024] [Indexed: 11/08/2024] Open
Abstract
Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 - ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6ANUC vs. ER r = 0.2373 and KAT6BNUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.
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Affiliation(s)
- Mateusz Olbromski
- Department of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, Wroclaw, 50-368, Poland.
| | - Monika Mrozowska
- Department of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, Wroclaw, 50-368, Poland
| | - Beata Smolarz
- Department of Pathology, Polish Mother's Memorial Hospital Research Institute, 281/289 Rzgowska St, Lodz, 93-338, Poland
| | - Hanna Romanowicz
- Department of Pathology, Polish Mother's Memorial Hospital Research Institute, 281/289 Rzgowska St, Lodz, 93-338, Poland
| | - Agnieszka Rusak
- Department of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, Wroclaw, 50-368, Poland
| | - Aleksandra Piotrowska
- Department of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, Wroclaw, 50-368, Poland
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Sun Y, Zhang W, Li Y, Zhu J, Liu C, Luo L, Liu J, Zhang C. Multigenerational genetic effects of paternal cadmium exposure on ovarian granulosa cell apoptosis. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 262:115123. [PMID: 37315360 DOI: 10.1016/j.ecoenv.2023.115123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 05/20/2023] [Accepted: 06/07/2023] [Indexed: 06/16/2023]
Abstract
To explore whether paternal cadmium (Cd) exposure causes ovarian granulosa cell (GC) apoptosis in offspring and the multigenerational genetic effects. From postnatal day 28 (PND28) until adulthood (PND56), SPF male Sprague-Dawley (SD) rats were gavaged daily with varying concentrations of CdCl2. (0, 0.5, 2, and 8 mg/kg). After treatment, the F1 generation was produced by mating with untreated female rats, and the F1 generation male rats were mated with untreated female rats to produce the F2 generation. Apoptotic bodies (electron microscopy) and significantly higher apoptotic rates (flow cytometry) were observed in both F1 and F2 ovarian GCs following paternal Cd exposure. Moreover, the mRNA (qRTPCR) or protein (Western blotting) levels of bax, bcl2, bcl-xl, caspase 3, caspase 8, and caspase 9 were changed to varying degrees. Apoptosis-related miRNAs (qRTPCR) and methylation modifications of apoptosis-related genes (bisulfite-sequencing PCR) in ovarian GCs were further detected. Compared with those of controls, the expression patterns of miRNAs in F1 and F2 offspring were different after paternal Cd exposure, while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, there are paternal genetic intergenerational and transgenerational effects on ovarian GC apoptosis induced by paternal Cd exposure. These genetic effects were related to the upregulation of BAX, BCL-XL, Cle-CASPASE 3, and Cle-CASPASE 9 in F1 and the upregulation of Cle-CASPASE 3 in F2 progeny. Important changes in apoptosis-related miRNAs were also observed.
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Affiliation(s)
- Yi Sun
- Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environmental Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China; Key Laboratory of Environment and Female Reproductive Health, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Wenchang Zhang
- Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environmental Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China.
| | - Yuchen Li
- Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environmental Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China
| | - Jianlin Zhu
- Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environmental Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China
| | - Chenchen Liu
- Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environmental Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China
| | - Lingfeng Luo
- Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environmental Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China
| | - Jin Liu
- Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environmental Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian Province, China
| | - Chenyun Zhang
- School of Health Management, Fujian Medical University, Fuzhou 350122, Fujian Province, China.
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Karimi Dermani F, Datta I, Gholamzadeh Khoei S. MicroRNA-452: a double-edged sword in multiple human cancers. Clin Transl Oncol 2023; 25:1189-1206. [PMID: 36622551 DOI: 10.1007/s12094-022-03041-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 12/03/2022] [Indexed: 01/10/2023]
Abstract
MicroRNAs (miRNAs) are small, noncoding RNAs with important functions in development, cell differentiation, and regulation of cell cycle and apoptosis. MiRNA expression is deregulated in various pathological processes including tumorigenesis and cancer progression through various mechanisms including amplification or deletion of miRNA genes, mutations, and epigenetic silencing and defects in the miRNA biogenesis machinery. Several studies have now shown abnormal miRNA profiles and proved their involvement in the initiation and progression of cancer. Since miR-452 has diverse roles (as suppressor or oncogene) in different cellular processes including epithelial-mesenchymal transition (EMT), proliferation, migration, and invasion, in this review we highlight a brief overview of the biological function and regulatory mechanism of miR-452 and its involvement as a potential biomarker for diagnosis and treatment of various cancer types.
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Affiliation(s)
| | - Ishwaree Datta
- Department of Biological Science, Florida State University, Tallahassee, FL, USA
| | - Saeideh Gholamzadeh Khoei
- Clinical Research Development Unit, Kowsar Hospital, Qazvin University of Medical Sciences, Qazvin, Iran.
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Cheng W, Luan P, Jin X. circUBAP2 inhibits cisplatin resistance in gastric cancer via miR-300/KAT6B axis. Anticancer Drugs 2023; 34:126-134. [PMID: 36206113 DOI: 10.1097/cad.0000000000001391] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Circular RNAs play an important role in regulating cisplatin (CDDP) resistance in gastric cancer (GC). The aim of this study was to examine the role and downstream regulation mechanisms of circUBAP2 in CDDP resistance of GC. The expression of circUBAP2 in GC and its correlation with the prognosis of GC patients were analyzed using qRT-PCR and the Kaplan-Meier plotter database. The effects of circUBAP2 on cell viability and apoptosis were investigated by Cell Counting Kit 8 assay and flow cytometry. The expressions of drug-resistance-related proteins, P-gp and MRP1, were detected by Western blot. The interaction between circUBAP2 and miR-300 was confirmed using RNA pulldown and immunoprecipitation assays. The correlation between miR-300 and KAT6B was assessed using dual-luciferase reporter assay and TCGA database. CircUBAP2 was downregulated in GC tissues and cell lines, and correlated with the poor prognosis of GC. In addition, circUBAP2 enhanced apoptosis but inhibited cell viability and the CDDP resistance of GC cells in vitro . CircUBAP2 acted as a sponge of microRNA-300 (miR-300) and was negatively correlated with miR-300. Moreover, the upregulation of miR-300 partially removed the effects of circUBAP2 on cell viability, apoptosis and CDDP resistance in GC cells. MiR-300 directly targeted to lysine acetyltransferase 6B (KAT6B), and KAT6B overexpression showed an inhibitory effect on cell viability and CDDP resistance of GC cells. Our data suggested that the circUBAP2/miR-300/KAT6B axis was involved in the inhibition of CDDP resistance in GC, which might provide a novel focus for potential GC therapy.
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Affiliation(s)
- Weicai Cheng
- Department of Gastrointestinal Surgery, Yantaishan Hospital, Yantai, China
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Zhang LH, Zhuo HQ, Hou JJ, Zhou Y, Cheng J, Cai JC. Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis. World J Gastrointest Oncol 2022; 14:2097-2107. [PMID: 36438703 PMCID: PMC9694269 DOI: 10.4251/wjgo.v14.i11.2097] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 06/16/2022] [Accepted: 10/17/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Proteomic signatures of Ming's infiltrative gastric cancer (IGC) remain unknown. AIM To elucidate the molecular characteristics of IGC at the proteomics level. METHODS Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performance liquid chromatography tandem mass spectrometry. The identified peptides were sequenced de novo and matched against the SwissProt database using Maxquant software. The differentially expressed proteins (DEPs) were screened using |log2(Fold change)| > 1 and P-adj < 0.01 as the thresholds. The expression levels of selected proteins were verified by Western blotting. The interaction network of the DEPs was constructed with the STRING database and visualized using Cytoscape with cytoHubba software. The DEPs were functionally annotated using clusterProfiler, STRING and DAVID for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. P < 0.05 was considered statistically significant. RESULTS A total of 7361 DEPs were identified, of which 94 were significantly up-regulated and 223 were significantly down-regulated in IGC relative to normal gastric tissues. The top 10 up-regulated proteins were MRTO4, BOP1, PES1, WDR12, BRIX1, NOP2, POLR1C, NOC2L, MYBBP1A and TSR1, and the top 10 down-regulated proteins were NDUFS8, NDUFS6, NDUFA8, NDUFA5, NDUFC2, NDUFB8, NDUFB5, NDUFB9, UQCRC2 and UQCRC1. The up-regulated proteins were enriched for 9 biological processes including DNA replication, ribosome biogenesis and initiation of DNA replication, and the cellular component MCM complex. Among the down-regulated proteins, 17 biological processes were enriched, including glucose metabolism, pyruvic acid metabolism and fatty acid β-oxidation. In addition, the mitochondrial inner membrane, mitochondrial matrix and mitochondrial proton transport ATP synthase complex were among the 6 enriched cellular components, and 11 molecular functions including reduced nicotinamide adenine dinucleotide dehydrogenase activity, acyl-CoA dehydrogenase activity and nicotinamide adenine dinucleotide binding were also enriched. The significant KEGG pathways for the up-regulated proteins were DNA replication, cell cycle and mismatch repair, whereas 18 pathways including oxidative phosphorylation, fatty acid degradation and phenylalanine metabolism were significantly enriched among the down-regulated proteins. CONCLUSION The proteins involved in cell cycle regulation, DNA replication and mismatch repair, and metabolism were significantly altered in IGC, and the proteomic profile may enable the discovery of novel biomarkers.
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Affiliation(s)
- Li-Hua Zhang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
- Institute of Gastrointestinal Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
| | - Hui-Qin Zhuo
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian Province, China
| | - Jing-Jing Hou
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian Province, China
| | - Yang Zhou
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
- Institute of Gastrointestinal Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
| | - Jia Cheng
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian Province, China
| | - Jian-Chun Cai
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
- Institute of Gastrointestinal Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian Province, China
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Wang Z, Liu J, Xie J, Yuan X, Wang B, Shen W, Zhang Y. Regulation of autophagy by non-coding RNAs in gastric cancer. Front Oncol 2022; 12:947332. [PMID: 36353541 PMCID: PMC9637602 DOI: 10.3389/fonc.2022.947332] [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: 05/18/2022] [Accepted: 07/18/2022] [Indexed: 11/22/2023] Open
Abstract
Autophagy is a conserved cellular self-digesting process that degrades obsoleting proteins and cellular components and plays a crucial role in the tumorigenesis, metastasis, and drug resistance of various tumors such as gastric cancer (GC). As a hotspot in molecular biology, non-coding RNAs (ncRNAs) are involved in the regulation of multiple biological processes, such as autophagy. Increasing evidence indicate that various ncRNAs exert double roles in the initiation and progression of GC, either serve as oncogenes or tumor suppressors. Recent studies have shown that some ncRNAs could modulate autophagy activity in GC cells, which would affect the malignant transformation and drug resistance. Whether the function of ncRNAs in GC is dependent on autophagy is undefined. Therefore, identifying the underlying moleculr targets of ncRNAs in autophagy pathways and the role of ncRNA-regulated autophagy in GC could develop new treatment interventions for this disease. This review summarizes the autophagy process and its role in GC, and the regulatory mechanisms of ncRNAs, as well as focuses on the dual role of ncRNAs-mediated autophagy in GC, for the development of potential therapeutic strategies in GC patients.
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Affiliation(s)
- Zijian Wang
- Graduate College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jiarui Liu
- College of Life Science and Technology, Guangxi University, Nanning, China
| | - Jingri Xie
- Department of Gastroenterology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xingxing Yuan
- Graduate College, Heilongjiang University of Chinese Medicine, Harbin, China
- Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, China
| | - Bingyu Wang
- Graduate College, Heilongjiang University of Chinese Medicine, Harbin, China
- Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, China
| | - Wenjuan Shen
- Department of Gynaecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yang Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
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Zhou X, Lin J, Wang F, Chen X, Zhang Y, Hu Z, Jin X. Circular RNA-regulated autophagy is involved in cancer progression. Front Cell Dev Biol 2022; 10:961983. [PMID: 36187468 PMCID: PMC9515439 DOI: 10.3389/fcell.2022.961983] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 08/03/2022] [Indexed: 12/05/2022] Open
Abstract
Circular RNAs (circRNAs) are a sort of long, non-coding RNA molecules with a covalently closed continuous ring structure without 5'-3' polarity and poly-A tail. The modulative role of circRNAs in malignant diseases has been elucidated by many studies in recent years via bioinformatics and high-throughput sequencing technologies. Generally, circRNA affects the proliferative, invasive, and migrative capacity of malignant cells via various mechanisms, exhibiting great potential as novel biomarkers in the diagnoses or treatments of malignancies. Meanwhile, autophagy preserves cellular homeostasis, serving as a vital molecular process in tumor progression. Mounting studies have demonstrated that autophagy can not only contribute to cancer cell survival but can also induce autophagic cell death in specific conditions. A growing number of research studies have indicated that there existed abundant associations between circRNAs and autophagy. Herein, we systemically reviewed and discussed recent studies on this topic in different malignancies and concluded that the circRNA–autophagy axis played crucial roles in the proliferation, metastasis, invasion, and drug or radiation resistance of different tumor cells.
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Lu L, Liang Q, Zhang X, Xu Y, Meng D, Liang Z. Autophagy Related Noncoding RNAs: Emerging Regulatory Factors of Gastric Cancer. Cancer Manag Res 2022; 14:2215-2224. [PMID: 35898946 PMCID: PMC9309173 DOI: 10.2147/cmar.s364761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 07/12/2022] [Indexed: 11/29/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant cancers that seriously affect human health. Autophagy is a highly conserved self-defense mechanism found to plays an important role in the occurrence, progression, drug resistance, and prognosis of GC. Noncoding RNAs (ncRNAs) play a critical role in the occurrence and development of a variety of diseases including GC. In recent years, increasing attention has been given to research on autophagy-related ncRNAs, such as miRNA, lncRNA, and circRNA in GC. Herein, we briefly summarize the roles, functions, and the research progress of autophagy and autophagy-related ncRNAs in GC with a focus on the potential application in GC tumorigenesis, development, prognosis, and drug resistance. We also discussed prospects of clinical application, future research direction, and challenges in future research of autophagy-related ncRNAs.
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Affiliation(s)
- Ling Lu
- Child Healthcare Department, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
| | - Qiaoyan Liang
- Health Care Department, People’s Liberation Army Navy No. 971 Hospital, Qingdao, People’s Republic of China
| | - Xinyi Zhang
- School of Medicine, Jiangsu University, Zhenjiang, People’s Republic of China
| | - Yumeng Xu
- School of Medicine, Jiangsu University, Zhenjiang, People’s Republic of China
| | - Dehua Meng
- Department of Allergy, Dongtai People’s Hospital, Yancheng, People’s Republic of China
| | - Zhaofeng Liang
- School of Medicine, Jiangsu University, Zhenjiang, People’s Republic of China
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Yang Q, Chen Y, Guo R, Dai Y, Tang L, Zhao Y, Wu X, Li M, Du F, Shen J, Yi T, Xiao Z, Wen Q. Interaction of ncRNA and Epigenetic Modifications in Gastric Cancer: Focus on Histone Modification. Front Oncol 2022; 11:822745. [PMID: 35155211 PMCID: PMC8826423 DOI: 10.3389/fonc.2021.822745] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 12/28/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer has developed as a very common gastrointestinal tumors, with recent effective advancements in the diagnosis and treatment of early gastric cancer. However, the prognosis for gastric cancer remains poor. As a result, there is in sore need of better understanding the mechanisms of gastric cancer development and progression to improve existing diagnostic and treatment options. In recent years, epigenetics has been recognized as an important contributor on tumor progression. Epigenetic changes in cancer include chromatin remodeling, DNA methylation and histone modifications. An increasing number of studies demonstrated that noncoding RNAs (ncRNAs) are associated with epigenetic changes in gastric cancer. Herein, we describe the molecular interactions of histone modifications and ncRNAs in epigenetics. We focus on ncRNA-mediated histone modifications of gene expression associated with tumorigenesis and progression in gastric cancer. This molecular mechanism will contribute to our deeper understanding of gastric carcinogenesis and progression, thus providing innovations in gastric cancer diagnosis and treatment strategies.
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Affiliation(s)
- Qingfan Yang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.,South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Yu Chen
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Rui Guo
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China
| | - Yalan Dai
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.,South Sichuan Institute of Translational Medicine, Luzhou, China
| | - Liyao Tang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Yueshui Zhao
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Xu Wu
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Mingxing Li
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Fukuan Du
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Jing Shen
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Tao Yi
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, China
| | - Zhangang Xiao
- South Sichuan Institute of Translational Medicine, Luzhou, China.,Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, China
| | - Qinglian Wen
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China.,South Sichuan Institute of Translational Medicine, Luzhou, China
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11
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Li J, Zhao Z, Wang X, Ma Q, Ji H, Wang Y, Yu R. PBX2-Mediated circTLK1 Activates JAK/STAT Signaling to Promote Gliomagenesis via miR-452-5p/SSR1 Axis. Front Genet 2021; 12:698831. [PMID: 34721518 PMCID: PMC8554161 DOI: 10.3389/fgene.2021.698831] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 08/18/2021] [Indexed: 12/05/2022] Open
Abstract
Glioma is considered one of the most lethal brain tumors, as the aggressive blood vessel formation leads to high morbidity and mortality rates. However, the mechanisms underlying the initiation and progression of glioma remain unclear. Here, we aimed to reveal the role of circTLK1 in glioma development. Our results revealed that circTLK1 is highly expressed in glioma tumor tissues and glioma cell lines. We then conducted a series of experiments that showed that circTLK1 was involved in the progression of gliomas. Mechanistically, investigation of the factors downstream of circTLK1 revealed that circTLK1 activated JAK/STAT signaling in glioma cells. Furthermore, AGO2-RIP, RNA-pull down, and luciferase reporter gene assays led to the identification of the novel circTLK1/miR-452-5p/SSR1 axis. Moreover, we investigated the upstream regulator of circTLK1 and found that circTLK1 expression in glioma cells could be regulated by the transcriptional factor PBX2. Taken together, our findings show that circTLK1 mediated by PBX2 activates JAK/STAT signaling to promote glioma progression through the miR-452-5p/SSR1 pathway. These results provide new insights into glioma diagnosis and therapy.
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Affiliation(s)
- Jing Li
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China.,Department of Neurosurgery, Second People's Hospital of Huai'an City, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, China
| | - Zongren Zhao
- Department of Neurosurgery, Second People's Hospital of Huai'an City, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, China
| | - Xiang Wang
- Department of Rehabilitation, The Affiliated Xuzhou Rehabilitation Hospital of Xuzhou Medical University, Xuzhou, China
| | - Qiong Ma
- Jiangsu College of Nursing, Huai'an, China
| | - Huanhuan Ji
- Department of Neurosurgery, Second People's Hospital of Huai'an City, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, China
| | - Yan Wang
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China
| | - Rutong Yu
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, China
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12
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Jiang J, Wang HJ, Mou XZ, Zhang H, Chen Y, Hu ZM. Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma. Technol Cancer Res Treat 2021; 20:15330338211033063. [PMID: 34464167 PMCID: PMC8411621 DOI: 10.1177/15330338211033063] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Aims: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase
implicated to have a role in tumor suppression. However, the relationship
between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of
this study was to detect the expression of KAT6B in HCC tissues and analyze
its connection with the clinicopathological features of HCC. Methods: First, we performed immunohistochemical staining on 250 HCC tissues and 222
non-tumor liver tissues to examine the expression of KAT6B.Then the relation
between KAT6B expression and clinicopathological parameters was analyzed by
chi-square test, and the overall survival analysis was conducted by
Kaplan-Meier survival method. In addition, based on the Oncomine expression
array online and the UALCAN database, we compared KAT6B expression
differences between normal liver tissues and HCC tissues more broadly. Results: Compared with normal tissues, KAT6B expression was significantly lower in HCC
tissues. Low KAT6B expression was found to be related to gender, AFP level,
and tumor size. According to the online database, KAT6B expression was found
to be decreased in HCC tissues and high in normal tissues. Conclusions: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B
may be a potential tumor suppressor in liver cancer.
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Affiliation(s)
- Junjie Jiang
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.,Clinical Research Institute, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China.,Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China.,Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China
| | - Hui-Ju Wang
- Clinical Research Institute, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China.,Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China
| | - Xiao-Zhou Mou
- Clinical Research Institute, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China.,Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China
| | - Huanqing Zhang
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.,Clinical Research Institute, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China.,Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China.,Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China
| | - YiZhen Chen
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.,Clinical Research Institute, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China.,Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China.,Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China
| | - Zhi-Ming Hu
- Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China
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13
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Wang Y, Mo Y, Peng M, Zhang S, Gong Z, Yan Q, Tang Y, He Y, Liao Q, Li X, Wu X, Xiang B, Zhou M, Li Y, Li G, Li X, Zeng Z, Guo C, Xiong W. The influence of circular RNAs on autophagy and disease progression. Autophagy 2021; 18:240-253. [PMID: 33904341 DOI: 10.1080/15548627.2021.1917131] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Circular RNAs (circRNAs) are non-coding RNAs that have attracted considerable attention in recent years. Owing to their distinct circular structure, circRNAs are stable in cells. Autophagy is a catabolic process that helps in the degradation and recycling of harmful or inessential biological macromolecules in cells and enables cells to adapt to stress and changes in the internal and external environments. Evidence has shown that circRNAs influence the course of a disease by regulating autophagy, which indicates that autophagy is involved in the onset and development of various diseases and can affect drug resistance (for example, it affects cisplatin resistance in tumors). In this review, we summarized the role of circRNAs in autophagy and their influence on disease onset and progression as well as drug resistance. The review will expand our understanding of tumors as well as cardiovascular and neurological diseases and also suggest novel therapeutic strategies.Abbreviations: ACR: autophagy-related circRNA; ADSCs: adipogenic mesenchymal stem cells; AMPK: AMP-activated protein kinase; ATG: autophagy related; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; ceRNA: competing endogenous RNA; circRNA: circular RNA; CMA: chaperone-mediated autophagy; EPCs: endothelial progenitor cells; LE/MVBs: late endosomes/multivesicular bodies; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NSCLC: non-small cell lung cancer; PDLSCs: periodontal ligament stem cells; PE: phosphatidylethanolamine; PtdIns: phosphatidylinositol; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate 1,2-dipalmitoyl; PTEN: phosphatase and tensin homolog; RBPs: RNA-binding proteins; SiO2: silicon dioxide; TFEB: transcription factor EB; ULK: unc-51 like autophagy activating kinase 1.
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Affiliation(s)
- Yian Wang
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Yongzhen Mo
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Miao Peng
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Shanshan Zhang
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhaojian Gong
- Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Qijia Yan
- Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yanyan Tang
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Yi He
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Qianjin Liao
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Xiayu Li
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xu Wu
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Bo Xiang
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Ming Zhou
- Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Yong Li
- Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Guiyuan Li
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Xiaoling Li
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Zhaoyang Zeng
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Can Guo
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
| | - Wei Xiong
- NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.,Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China
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14
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Zhang S, Liu J, Yuan T, Liu H, Wan C, Le Y. Circular RNA 0001313 Knockdown Suppresses Non-Small Cell Lung Cancer Cell Proliferation and Invasion via the microRNA-452/HMGB3/ERK/MAPK Axis. Int J Gen Med 2020; 13:1495-1507. [PMID: 33328759 PMCID: PMC7735797 DOI: 10.2147/ijgm.s272996] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/10/2020] [Indexed: 12/19/2022] Open
Abstract
Background Non-small cell lung cancer (NSCLC) seriously endangers human health. Circular RNAs (circRNAs) regulate diverse types of cancers, including NSCLC. This study investigated the possible mechanism of circ0001313 in NSCLC. Materials and Methods Circ0001313 expression in NSCLC tissues was measured, and its correlation with clinicopathological features was analyzed. The binding relationships among circ0001313, microRNA (miR)-452 and HMGB3 were tested. The gain and loss of functions were performed to examine NSCLC cell malignant behaviors. After HMGB3 overexpression, ERK/MAPK pathway-related protein levels were detected. Subsequently, the rescue experiment was further performed using an ERK/MAPK pathway inhibitor PD98059. Results Abnormally elevated circ0001313 and decreased miR-452 in NSCLC cells were observed. Circ0001313 silencing or miR-452 overexpression significantly reduced NSCLC cell proliferation and invasion. Circ0001313 competitively bound to miR-452 to upregulate HMGB3, thus promoting NSCLC cell growth. HMGB3 overexpression activated the ERK/MAPK pathway to contribute to NSCLC development. Conclusion We highlighted that silencing of circ0001313 blunted the ERK/MAPK pathway via the miR-452/HMGB3 axis, thereby inhibiting NSCLC cell proliferation and invasion.
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Affiliation(s)
- Shihao Zhang
- Department of Respiratory and Critical Care Medicine, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, People's Republic of China
| | - Jiansheng Liu
- Department of Respiratory and Critical Care Medicine, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, People's Republic of China
| | - Taiwen Yuan
- Department of Respiratory and Critical Care Medicine, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, People's Republic of China
| | - Huiyu Liu
- Department of Respiratory and Critical Care Medicine, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, People's Republic of China
| | - Chengwei Wan
- Department of Respiratory and Critical Care Medicine, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, People's Republic of China
| | - Yonghong Le
- Department of Respiratory and Critical Care Medicine, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, People's Republic of China
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