miR-1229-3p as a Prognostic Predictor Facilitates Cell Viability, Migration, and Invasion of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) remains one of the most prevalent human malignancies with high mortality. Increasing studies have revealed microRNAs (miRNAs) play crucial roles in the tumorigenesis and progression of cancers. The current study investigated the expression levels of miR-1229-3p and its potential role in HCC. This study enrolled 121 HCC patients. The expression of miR-1229-3p was measured using RT-qPCR in HCC tissue samples and cell lines. The association of miR-1229-3p expression with clinical parameters and patients’ prognosis was analyzed by χ² test, Kaplan–Meier, and multivariate Cox regression analyses, respectively. The functions of miR-1229-3p in HCC cells were explored by CCK-8 assay, Transwell migration, and invasion assays. miR-1229-3p was upregulated in HCC tissue samples and cell lines. The upregulation of miR-1229-3p was related to positive lymph node metastasis and advanced TNM stages and predicted with patients’ poor prognosis. Overexpression of miR-1229-3p facilitated cell viability and metastasis of HCC cells while knockdown of miR-1229-3p suppressed cell viability and metastasis of HCC cells in vitro. miR-1229-3p may function as an oncogenic role in HCC via promoting cell viability and metastasis. Moreover, miR-1229-3p may be a predictive marker for tumor development and prognosis of HCC patients.

Key words

hepatocellular carcinoma - miR-1229-3p - migration - invasion - viability

Publication History

Received: 27 July 2021

Accepted after revision: 08 September 2021

Article published online:
05 November 2021

• References

• 1 Ferlay J, Colombet M, Soerjomataram I. et al Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; 103: 356-387
• 2 Xiong DD, Feng ZB, Lai ZF. et al High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma. Cell Death Disease 2019; 10: 658
• 3 Shen S, Lin Y, Yuan X. et al Biomarker microRNAs for diagnosis, prognosis and treatment of hepatocellular carcinoma: a functional survey and comparison. Sci Rep 2016; 6: 38311
• 4 Mak LY, Cruz-Ramón V, Chinchilla-López P. et al Global epidemiology, prevention, and management of hepatocellular carcinoma. Am Soc Clin Oncol Educ Book 2018; 38: 262-279
• 5 Allemani C, Matsuda T, Di Carlo V. et al Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 2018; 391: 1023-1075
• 6 He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5: 522-531
• 7 Han M, Li N, Li F. et al MiR-27b-3p exerts tumor suppressor effects in esophageal squamous cell carcinoma by targeting Nrf2. Hum Cell 2020; 33: 641-651
• 8 Ma B, Ma J, Yang Y. et al Effects of miR-330-3p on invasion, migration and EMT of gastric cancer cells by targeting PRRX1-mediated Wnt/b-catenin signaling pathway. Onco Targets Ther 2020; 13: 3411-3423
• 9 Zhu WJ, Yan Y, Zhang JW. et al Effect and mechanism of miR-26a-5p on proliferation and apoptosis of hepatocellular carcinoma cells. Cancer Manag Res 2020; 12: 3013-3022
• 10 Lv J, Zhu Y, Zhang Q. An increased level of MiR-222-3p is associated with TMP2 suppression, ERK activation and is associated with metastasis and a poor prognosis in renal clear cell carcinoma. Cancer Biomark 2020; 28: 141-149
• 11 Ma Y, Ma M, Ma L. et al Downregulation of miR-552 in hepatocellular carcinoma inhibits cell migration and invasion, and promotes cell apoptosis via RUNX3. Exp Ther Med 2019; 18: 3829-3836
• 12 Wang J, Chen J, Sun F. et al miR-202 functions as a tumor suppressor in hepatocellular carcinoma by targeting HK2. Oncol Lett 2020; 19: 2265-2271
• 13 Dégano IR, Camps-Vilaró A. Association of circulating microRNAs with coronary artery disease and usefulness for reclassification of healthy individuals: the REGICOR study. J Clin Med 2020; 9: 1402
• 14 Elosua R, Fitó M, Marrugat J. et al Identification of differentially expressed genes through integrated study of Alzheimer's disease affected brain regions. J Clin Med 2016; 11: e0152342
• 15 Trilla-Fuertes L, Miranda N, Castellano D. et al miRNA profiling in renal carcinoma suggest the existence of a group of pro-angionenic tumors in localized clear cell renal carcinoma. PloS one 2020; 15: e0229075
• 16 Zheng J, Sadot E, Vigidal JA. et al Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing. PLoS One 2018; 13: e0200776
• 17 Liao X, Wang X, Huang K. et al Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma. J Cancer 2019; 10: 3267-3283
• 18 Mohamed AA, Omar AAA, El-Awady RR. et al MiR-155 and MiR-665 role as potential non-invasive biomarkers for hepatocellular carcinoma in Egyptian patients with chronic hepatitis C virus infection. J Transl Int Med 2020; 8: 32-40
• 19 Yan L, Yue C, Xu Y. et al Identification of potential diagnostic and prognostic pseudogenes in hepatocellular carcinoma based on pseudogene-miRNA-mRNA competitive network. Med Sci Monit 2020; 26: e921895
• 20 Ghanbari M, Ikram MA, de Looper HWJ. et al Genome-wide identification of microRNA-related variants associated with risk of Alzheimer's disease. Sci Rep 2016; 6: 28387
• 21 Butkytė S, Čiupas L, Jakubauskienė E. et al Splicing-dependent expression of microRNAs of mirtron origin in human digestive and excretory system cancer cells. Clin Epigenetics 2016; 8: 33
• 22 Nishibeppu K, Komatsu S, Imamura T. Plasma microRNA profiles: identification of miR-1229-3p as a novel chemoresistant and prognostic biomarker in gastric cancer. Sci Rep 2020; 10: 3161
• 23 Cao Q, Shi Y, Wang X. et al Circular METRN RNA hsa_circ_0037251 promotes glioma progression by sponging miR-1229-3p and regulating mTOR expression. Sci Rep 2019; 9: 19791
• 24 Zhao X, Cui L. A robust six-miRNA prognostic signature for head and neck squamous cell carcinoma. J Cell Physiol 2020; 235: 8799-8811
• 25 Tan Z, Zheng H, Liu X. et al MicroRNA-1229 overexpression promotes cell proliferation and tumorigenicity and activates Wnt/b-catenin signaling in breast cancer. Oncotarget 2016; 7: 24076-24087
• 26 Hu HY, Yu CH, Zhang HH. et al Exosomal miR-1229 derived from colorectal cancer cells promotes angiogenesis by targeting HIPK2. Int J Biol Macromol 2019; 132: 470-477
• 27 Song W, Fu T. Circular RNA-associated competing endogenous RNA network and prognostic nomogram for patients with colorectal cancer. Front Oncol 2019; 9: 1181
• 28 Chen P, Duan X, Li X. et al HIPK2 suppresses tumor growth and progression of hepatocellular carcinoma through promoting the degradation of HIF-1α. Oncogene 2020; 39: 2863-2876