Long Noncoding RNA Cytoskeleton Regulator RNA Suppresses Apoptosis in Hepatoma Cells by Modulating the miR-125a-5p/HS1-Associated Protein X-1 Axis to Induce Caspase-9 Inactivation
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. Methods: The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosis-related proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. Results: CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells. miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. Conclusions: CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.
Abstract
Background/Aims: The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. Methods: The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosis-related proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. Results: CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells. miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. Conclusions: CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.
참고문헌 (30)
- Marengo A, "Liver cancer : connections with obesity, fatty liver, and cirrhosis", Annu Rev Med, 67, pp.103~117 (2016)
- El-Serag HB, "Hepatocellular carcinoma : epidemiology and molecular carcinogenesis", Gastroenterology, 132, pp.2557~2576 (2007)
- Janevska D, "Hepatocellular carcinoma : risk factors, diagnosis and treatment", Open Access Maced J Med Sci, 3, pp.732~736 (2015)
- Grandhi MS, "Hepatocellular carcinoma : from diagnosis to treatment", Surg Oncol, 25, pp.74~85 (2016)
- Budhu A, "Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment", Cancer Cell, 10, pp.99~111 (2006)
- Bhan A, "Long noncoding RNA and cancer : a new paradigm", Cancer Res, 77, pp.3965~3981 (2017)
- Cao WJ, "Analysis of long non-coding RNA expression profiles in gastric cancer", World J Gastroenterol, 19, pp.3658~3664 (2013)
- Liu S, "LncRNA CYTOR and MIR4435-2HG in ovarian cancer and its relationship with clinicopathological features", Panminerva Med, 64, pp.119~120 (2022)
- Li M, "lncRNA-CYTOR works as an oncogene through the CYTOR", miR-3679-5p, DNA Cell Biol, pp.2019, 38[DOI]
- Zhang J, "Long noncoding RNA CYTOR sponges miR-195 to modulate proliferation, migration, invasion and radiosensitivity in nonsmall cell lung cancer cells", Biosci Rep, 38, pp.BSR20181599~ (2018)
- Suzuki Y, "HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family tyrosine kinases", J Immunol, 158, pp.2736~2744 (1997)
- Yan J, "HAX-1 inhibits apoptosis in prostate cancer through the suppression of caspase-9 activation", Oncol Rep, 34, pp.2776~2781 (2015)
- Simmen T, "Hax-1 : a regulator of calcium signaling and apoptosis progression with multiple roles in human disease", Expert Opin Ther Targets, 15, pp.741~751 (2011)
- Li J, "Circular RNAs in cancer : novel insights into origins, properties, functions and implications", Am J Cancer Res, 5, pp.472~480 (2015)
- Ming M, "miRNA-125a-5p inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting TP53 regulated inhibitor of apoptosis 1 and Bcl-2-like-2 protein", Exp Ther Med, 18, pp.1196~1202 (2019)
- Cao SQ, "Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion", World J Gastroenterol, 25, pp.5283~5299 (2019)
- Liu J, "Identification of key genes and long non-coding RNA associated ceRNA networks in hepatocellular carcinoma", PeerJ, 7, pp.e8021~ (2019)
- Li J, "HULC and Linc00152 act as novel biomarkers in predicting diagnosis of hepatocellular carcinoma", Cell Physiol Biochem, 37, pp.687~696 (2015)
- Deng X, "Linc00152 promotes cancer progression in hepatitis B virusassociated hepatocellular carcinoma", Biomed Pharmacother, 90, pp.100~108 (2017)
- Ma P, "LINC00152 promotes cell cycle progression in hepatocellular carcinoma via miR-193a", b-3p, Cell Cycle, pp.2018, 17[DOI]
- Wang J, "Insight into the molecular mechanism of LINC00152", miR-215, J Cell Biochem, pp.2019, 120[DOI]
- Tian Q, "lncRNA CYTOR promotes cell proliferation and tumor growth via miR-125b", SEMA4C axis in hepatocellular carcinoma, 2021, pp.22, 796~
- Xu X, "miR-125a-5p inhibits tumorigenesis in hepatocellular carcinoma", Aging(Albany NY), 11, pp.7639~7662 (2019)
- Liu Y, "Long non-coding RNA(lncRNA)CYTOR promotes hepatocellular carcinoma proliferation by targeting the microRNA-125a-5p", LASP1 axis, 2022, pp.13, 3666~3679
- He JH, "Analyzing the LncRNA, miRNA, and mRNA regulatory network in prostate cancer with bioinformatics software", J Comput Biol, 25, pp.146~157 (2018)
- Deng X, "HAX-1 protects glioblastoma cells from apoptosis through the Akt1 pathway", Front Cell Neurosci, 11, pp.420~ (2017)
- Wu G, "miR-100 reverses cisplatin resistance in breast cancer by suppressing HAX-1", Cell Physiol Biochem, 47, pp.2077~2087 (2018)
- Wang Y, "HAX-1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation", Int J Clin Exp Pathol, 8, pp.8099~8106 (2015)
- Hu YL, "HAX-1 promotes the migration and invasion of hepatocellular carcinoma cells through the induction of epithelial-mesenchymal transition via the NF-κB pathway", Exp Cell Res, 381, pp.66~76 (2019)
- Sun X, "MicroRNA-223increases the sensitivity of triple-negative breast cancer stem cells to TRAIL-induced apoptosis by targeting HAX-1", PLoS One, 11, pp.e0162754~ (2016)