Login Register Cart 0
Generic placeholder image

Current Signal Transduction Therapy

Editor-in-Chief

ISSN (Print): 1574-3624
ISSN (Online): 2212-389X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The Effect of Silencing MiR-4270 on Apoptosis in HCC Cell Line

Author(s): Hanieh Gholamia, Hassan Akrami*, Hosseinali Sassan, Nasrollah Erfani, Mohammad Reza Fattahi and Mojdeh Heidari

Volume 19, Issue 1, 2024

Published on: 21 December, 2023

Article ID: e211223224760 Pages: 8

DOI: 10.2174/0115743624264947231217161150

Price: $65

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common type of cancer. Although HCC treatment has greatly improved over the past few decades, patient survival rates are still very low. Therefore, it is essential to find new treatments for HCC. Apoptosis has been shown to be the most effective in disrupting cancer growth. Improper functioning of proteins in apoptosis can lead to cancer growth. MicroRNAs (miRNAs) are key regulators in the development and progression of HCC.

Objective: Irregular expression of miRNAs involved in apoptosis signaling can lead to tumorigenesis. Therefore, we investigated the effect of the hsa-miR-4270 inhibitor on cell proliferation and apoptosis.

Methods: HepG2 cells were cultured at 37°C and 95% air. Transfection of HepG2 cells was performed by miR-4270 inhibitor and lipofectamine 2000. Cell proliferation of HepG2 cells was determined with MTT assay and different concentrations of miR-4270 specific inhibitors. DNA laddering assay was performed to evaluate the induction of apoptosis. Finally, the transcription level of genes involved in apoptosis, including BAX, BCL2, Caspase3, and p53, was measured by real-time RT-PCR.

Results: The results of MTT and DNA laddering assays showed that the miR-4270 inhibitor declined cell proliferation and induced apoptosis in HepG2 cells. Also, the results of quantitative real-time RT-PCR indicated an upregulation of transcription of BAX, p53 and Caspase3 genes and a decline in expression of BCL2 gene.

Conclusion: Taken together, we found hsa-miR-4270 inhibitor decreased cell proliferation and induced apoptosis in the HepG2 cell line, which can be used as a new therapeutic strategy for HCC patients.

Graphical Abstract

[1]
Yang N, Ekanem NR, Sakyi CA, Ray SD. Hepatocellular carcinoma and microRNA: New perspectives on therapeutics and diagnostics. Adv Drug Deliv Rev 2015; 81: 62-74.
[http://dx.doi.org/10.1016/j.addr.2014.10.029] [PMID: 25450260]
[2]
Suna N, Boyacioglu A. Management of hepatocellular carcinoma: Prevention, surveillance, diagnosis, and staging. Exp Clin Transplant 2017; 15 (Suppl. 2): 31-5.
[3]
Massarweh NN, El-Serag HB. Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Cancer Contr 2017; 24(3)
[http://dx.doi.org/10.1177/1073274817729245] [PMID: 28975830]
[4]
Balogh J, Victor D III, Asham EH, et al. Hepatocellular carcinoma: A review. J Hepatocell Carcinoma 2016; 3: 41-53.
[http://dx.doi.org/10.2147/JHC.S61146] [PMID: 27785449]
[5]
Zhu HR, Huang RZ, Yu XN, et al. Microarray expression profiling of microRNAs reveals potential biomarkers for hepatocellular carcinoma. Tohoku J Exp Med 2018; 245(2): 89-98.
[http://dx.doi.org/10.1620/tjem.245.89] [PMID: 29899182]
[6]
O’Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol 2018; 9: 402.
[http://dx.doi.org/10.3389/fendo.2018.00402] [PMID: 30123182]
[7]
Mao B, Wang GE. MicroRNAs involved with hepatocellular carcinoma (Review). Oncol Rep 2015; 34(6): 2811-20.
[http://dx.doi.org/10.3892/or.2015.4275] [PMID: 26398882]
[8]
Koff J, Ramachandiran S, Bernal-Mizrachi L. A time to kill: Targeting apoptosis in cancer. Int J Mol Sci 2015; 16(2): 2942-55.
[http://dx.doi.org/10.3390/ijms16022942] [PMID: 25636036]
[9]
Huang Z, Luo Y, Chen C, et al. miR-325-3p reduces proliferation and promotes apoptosis of gastric cancer cells by inhibiting human antigen R. Can J Gastroenterol Hepatol 2023; 2023.
[10]
Gao H, Liu C. miR-429 represses cell proliferation and induces apoptosis in HBV-related HCC. Biomed Pharmacother 2014; 68(8): 943-9.
[http://dx.doi.org/10.1016/j.biopha.2014.09.005] [PMID: 25312821]
[11]
de la Cruz-Ojeda P, Schmid T, Boix L, et al. miR-200c-3p, miR-222-5p, and miR-512-3p constitute a biomarker signature of sorafenib effectiveness in advanced hepatocellular carcinoma. Cells 2022; 11(17): 2673.
[http://dx.doi.org/10.3390/cells11172673] [PMID: 36078082]
[12]
Mao Y, Chen W, Wu H, Liu C, Zhang J, Chen S. Mechanisms and functions of MiR-200 family in hepatocellular carcinoma. OncoTargets Ther 2021; 13: 13479-90.
[http://dx.doi.org/10.2147/OTT.S288791] [PMID: 33447052]
[13]
Feng X, Zou B, Nan T, et al. MiR-25 enhances autophagy and promotes sorafenib resistance of hepatocellular carcinoma via targeting FBXW7. Int J Med Sci 2022; 19(2): 257-66.
[http://dx.doi.org/10.7150/ijms.67352] [PMID: 35165511]
[14]
El-Naidany SS, Zid E, Reda F, Nada A, Fouda E. Clinical significance of MiR-130b and MiR-125b as biomarkers in hepatocellular carcinoma. Asian Pac J Cancer Prev 2022; 23(8): 2687-93.
[http://dx.doi.org/10.31557/APJCP.2022.23.8.2687] [PMID: 36037122]
[15]
Wei H, Wang J, Xu Z, et al. miR‐584‐5p regulates hepatocellular carcinoma cell migration and invasion through targeting KCNE2. Mol Genet Genomic Med 2019; 7(6): e702.
[http://dx.doi.org/10.1002/mgg3.702] [PMID: 31044566]
[16]
Zhang Y, Li M, Qiu Y, et al. miR-139-5p/ENAH affects progression of hepatocellular carcinoma cells. Biochem Genet 2022; 60(6): 2106-19.
[http://dx.doi.org/10.1007/s10528-022-10204-9] [PMID: 35254597]
[17]
Tao X, Yang X, Wu K, et al. miR-629–5p promotes growth and metastasis of hepatocellular carcinoma by activating β-catenin. Exp Cell Res 2019; 380(2): 124-30.
[http://dx.doi.org/10.1016/j.yexcr.2019.03.042] [PMID: 30954576]
[18]
Huang YH, Lian WS, Wang FS, et al. MiR-29a curbs hepatocellular carcinoma incidence via targeting of HIF-1α and ANGPT2. Int J Mol Sci 2022; 23(3): 1636.
[http://dx.doi.org/10.3390/ijms23031636] [PMID: 35163556]
[19]
Zhou D, Dong L, Yang L, et al. Identification and analysis of circRNA–miRNA–mRNA regulatory network in hepatocellular carcinoma. IET Syst Biol 2020; 14(6): 391-8.
[http://dx.doi.org/10.1049/iet-syb.2020.0061] [PMID: 33399102]
[20]
Liu Y, Corcoran M, Rasool O, et al. Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia. Oncogene 1997; 15(20): 2463-73.
[http://dx.doi.org/10.1038/sj.onc.1201643] [PMID: 9395242]
[21]
Li J, Tian H, Yang J, Gong Z. Long noncoding RNAs regulate cell growth, proliferation, and apoptosis. DNA Cell Biol 2016; 35(9): 459-70.
[http://dx.doi.org/10.1089/dna.2015.3187] [PMID: 27213978]
[22]
Davis CD, Emenaker NJ, Milner JA, Eds. Cellular proliferation, apoptosis and angiogenesis: Molecular targets for nutritional preemption of cancer. Seminars in oncology Semin Oncol. 2010; 37: pp. (3)243-57.
[23]
Liu Z, Wang Y, Dou C, et al. RETRACTED ARTICLE: MicroRNA-1468 promotes tumor progression by activating PPAR-γ-mediated AKT signaling in human hepatocellular carcinoma. J Exp Clin Cancer Res 2018; 37(1): 49.
[http://dx.doi.org/10.1186/s13046-018-0717-3] [PMID: 29510736]
[24]
Hamam R, Ali AM, Alsaleh KA, et al. microRNA expression profiling on individual breast cancer patients identifies novel panel of circulating microRNA for early detection. Sci Rep 2016; 6(1): 25997.
[http://dx.doi.org/10.1038/srep25997] [PMID: 27180809]
[25]
Tokuhisa M, Ichikawa Y, Kosaka N, et al. Exosomal miRNAs from peritoneum lavage fluid as potential prognostic biomarkers of peritoneal metastasis in gastric cancer. PLoS One 2015; 10(7): e0130472.
[http://dx.doi.org/10.1371/journal.pone.0130472] [PMID: 26208314]
[26]
Yao C, Sun M, Yuan Q, et al. MiRNA-133b promotes the proliferation of human Sertoli cells through targeting GLI3. Oncotarget 2016; 7(3): 2201-19.
[http://dx.doi.org/10.18632/oncotarget.6876] [PMID: 26755652]
[27]
Aminisepehr F, Babaei E, Hosseinpour Feizi MA. Study of the expression of miR-4270 in plasma of patients with breast invasive ductal carcinoma. Journal of Genetic Resources 2018; 4(2): 85-9.
[28]
Kepp O, Tesniere A, Schlemmer F, et al. Immunogenic cell death modalities and their impact on cancer treatment. Apoptosis 2009; 14(4): 364-75.
[http://dx.doi.org/10.1007/s10495-008-0303-9] [PMID: 19145485]
[29]
Shen D, Zhao H, Zeng P, et al. Circular RNA hsa_circ_0005556 accelerates gastric cancer progression by sponging miR-4270 to increase MMP19 expression. J Gastric Cancer 2020; 20(3): 300-12.
[http://dx.doi.org/10.5230/jgc.2020.20.e28] [PMID: 33024586]
[30]
Wang H, Huang Z, Zhao X, Guo B, Ji Z. miR-4270 regulates cell proliferation and apoptosis in patients with Sertoli cell-only syndrome by targeting GADD45A and inactivating the NOTCH signaling pathway. Am J Transl Res 2020; 12(9): 5730-40.
[PMID: 33042452]
[31]
Cai M, Shao W, Yu H, Hong Y, Shi L. paeonol inhibits cell proliferation, migration and invasion and induces apoptosis in hepatocellular carcinoma by regulating miR-21-5p/KLF6 axis. Cancer Manag Res 2020; 12: 5931-43.
[http://dx.doi.org/10.2147/CMAR.S254485] [PMID: 32765094]
[32]
Yang Y, Li M, Chang S, et al. MicroRNA-195 acts as a tumor suppressor by directly targeting Wnt3a in HepG2 hepatocellular carcinoma cells. Mol Med Rep 2014; 10(5): 2643-8.
[http://dx.doi.org/10.3892/mmr.2014.2526] [PMID: 25174704]
[33]
Wang Y, Chen F, Zhao M, et al. MiR-107 suppresses proliferation of hepatoma cells through targeting HMGA2 mRNA 3′UTR. Biochem Biophys Res Commun 2016; 480(3): 455-60.
[http://dx.doi.org/10.1016/j.bbrc.2016.10.070] [PMID: 27773820]
[34]
Zhang J-J, Wang C-Y, Hua L, Yao K-H, Chen J-T, Hu J-H. miR-107 promotes hepatocellular carcinoma cell proliferation by targeting Axin2. Int J Clin Exp Pathol 2015; 8(5): 5168-74.
[PMID: 26191213]
[35]
Fu X, Wen H, Jing L, et al. Micro RNA ‐155‐5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI 3K/Akt pathway. Cancer Sci 2017; 108(4): 620-31.
[http://dx.doi.org/10.1111/cas.13177] [PMID: 28132399]
[36]
Huo W, Du M, Pan X, Zhu X, Gao Y, Li Z. miR‐203a‐3p.1 targets IL ‐24 to modulate hepatocellular carcinoma cell growth and metastasis. FEBS Open Bio 2017; 7(8): 1085-91.
[http://dx.doi.org/10.1002/2211-5463.12248] [PMID: 28781949]
[37]
Sun G, Ding X, Bi N, et al. Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma. PLoS Genet 2019; 15(2): e1007888.
[http://dx.doi.org/10.1371/journal.pgen.1007888] [PMID: 30707694]
[38]
Li Y, Zhang Y, Zou Y, Duan S. The paradoxical roles of miR-4295 in human cancer: Implications in pathogenesis and personalized medicine. Genes Dis 2022; 9(3): 638-47.
[http://dx.doi.org/10.1016/j.gendis.2020.09.007] [PMID: 35782974]
[39]
Zhang L, Xu B, Qiang Y, et al. Overexpression of deubiquitinating enzyme USP 28 promoted non‐small cell lung cancer growth. J Cell Mol Med 2015; 19(4): 799-805.
[http://dx.doi.org/10.1111/jcmm.12426] [PMID: 25656529]
[40]
Zhang L, Wang H, Wang C. Persistence of smoking induced non‐small cell lung carcinogenesis by decreasing ERBB pathway‐related microRNA expression. Thorac Cancer 2019; 10(4): 890-7.
[http://dx.doi.org/10.1111/1759-7714.13020] [PMID: 30868748]
[41]
Ding M, Lin B, Li T, et al. A dual yet opposite growth-regulating function of miR-204 and its target XRN1 in prostate adenocarcinoma cells and neuroendocrine-like prostate cancer cells. Oncotarget 2015; 6(10): 7686-700.
[http://dx.doi.org/10.18632/oncotarget.3480] [PMID: 25797256]
[42]
Shen K, Cao Z, Zhu R, You L, Zhang T. The dual functional role of MicroRNA‐18a (miR‐18a) in cancer development. Clin Transl Med 2019; 8(1): e32.
[http://dx.doi.org/10.1186/s40169-019-0250-9] [PMID: 31873828]
[43]
Zhou Q, Anderson C, Hanus J, et al. Strand and cell type-specific function of microRNA-126 in angiogenesis. Mol Ther 2016; 24(10): 1823-35.
[http://dx.doi.org/10.1038/mt.2016.108] [PMID: 27203443]
[44]
Wang Y, Li C-f, Sun L-b. microRNA-4270-5p inhibits cancer cell proliferation and metastasis in hepatocellular carcinoma by targeting SATB2. Hum Cell 2020; 33(4): 1155-64.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy