Association Between Underexpression of Microrna-203 and Clinicopathological Significance in Hepatocellular Carcinoma Tissues

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2015 Jun 26

PMID 26109910

Citations 25

Authors

Yongru Liu

Fanghui Ren

Minhua Rong

Yihuan Luo

Yiwu Dang

Gang Chen

Affiliations

Soon will be listed here.

Abstract

Background: Although recent studies have shown the utility of miR-203 as a cancer-relevant biomarker, the validated clinical significance of miR-203 in HCC remains obscure. The aim of the present study was to evaluate the relationship between miR-203 expression and clinicopathological features in HCC patients.

Methods: MiR-203 expression in 95 formalin-fixed, paraffin embedded (FFPE) HCC tissues and their paired adjacent non-cancerous tissues was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Simultaneously, expression of miR-203 and its correlation with a variety of clinicopathological parameters and patient recurrence was analyzed.

Results: The relative level of miR-203 was 1.1651 ± 0.70378 in HCC tissues, significantly lower than its expression in the corresponding adjacent non-cancerous liver tissues (2.2408 ± 0.75351, P < 0.001). The area under curve (AUC) of low miR-203 expression to diagnose HCC was 0.85 (95 % CI: 0.796 ~ 0.904, P = 0.027) at a cut-off value 1.99 evaluated by the median expression of miR-203 in all tissues, including HCC and normal liver tissues. Expression of miR-203 was negatively correlated to metastasis (r = -0.254, P = 0.013), clinical tumor nodes metastasis (TNM) stage (r = -0.300, P = 0.003), nm23 expression (r = -0.292, P = 0.004), p21 expression (r = -0.223, P = 0.030), microvessel density (MVD)(r = -0.206, P = 0.045) and was positively correlated to cirrhosis (r = 0.487, P < 0.001). Additionally, the recurrent time of lower miR-203 expression group was 57.949 ± 4.184 months, slightly longer than that in the high expression group (54.682 ± 2.591 months), however, no significant difference was noted (Chi-square = 0.206, P = 0.650).

Conclusions: MiR-203 plays a vital role in the carcinogenesis and progression of HCC, which makes itself as a predictor for the deterioration of HCC. Furthermore, miR-203 may become a new target for molecular therapy in HCC.

Citing Articles

Bio-diagnostic performances of microRNAs set related to DNA damage response pathway among hepatitis C virus-associated hepatocellular carcinoma patients.

Abdo S, Shousha W, Mohamed A, Elshobaky M, Saleh M, Ali M J Genet Eng Biotechnol. 2023; 21(1):85.

PMID: 37587273 PMC: 10432369. DOI: 10.1186/s43141-023-00537-2.

microRNA-203 functions as a natural Ras inhibitor in hepatocellular carcinoma.

Guo J, Li L, Deng N, Xu Y, Wang G, Luo H Am J Cancer Res. 2023; 13(4):1295-1309.

PMID: 37168327 PMC: 10164818.

Comprehensive Analysis of Genes Associated With Sudden Infant Death Syndrome.

Mehboob R, Kurdi M, Ahmad M, Gilani S, Khalid S, Nasief H Front Pediatr. 2021; 9:742225.

PMID: 34722422 PMC: 8555024. DOI: 10.3389/fped.2021.742225.

Dysregulated microRNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Potential as Biomarkers and Therapeutic Targets.

Xu J, An P, Winkler C, Yu Y Front Oncol. 2020; 10:1271.

PMID: 32850386 PMC: 7399632. DOI: 10.3389/fonc.2020.01271.

Limonoid compounds from Xylocarpus granatum and their anticancer activity against esophageal cancer cells.

Jing L, Feng L, Zhou Z, Shi S, Deng R, Wang Z Thorac Cancer. 2020; 11(7):1817-1826.

PMID: 32449599 PMC: 7327699. DOI: 10.1111/1759-7714.13455.

References

Liang T, Chen E, Tang H . Hepatitis B virus gene mutations and hepatocarcinogenesis. Asian Pac J Cancer Prev. 2013; 14(8):4509-13. DOI: 10.7314/apjcp.2013.14.8.4509. View

Rong M, He R, Dang Y, Chen G . Expression and clinicopathological significance of miR-146a in hepatocellular carcinoma tissues. Ups J Med Sci. 2013; 119(1):19-24. PMC: 3916713. DOI: 10.3109/03009734.2013.856970. View

Schetter A, Leung S, Sohn J, Zanetti K, Bowman E, Yanaihara N . MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008; 299(4):425-36. PMC: 2614237. DOI: 10.1001/jama.299.4.425. View

Li J, Chen Y, Zhao J, Kong F, Zhang Y . miR-203 reverses chemoresistance in p53-mutated colon cancer cells through downregulation of Akt2 expression. Cancer Lett. 2011; 304(1):52-9. DOI: 10.1016/j.canlet.2011.02.003. View

Murata S, Mine T, Ueda T, Nakazawa K, Onozawa S, Yasui D . Transcatheter arterial chemoembolization based on hepatic hemodynamics for hepatocellular carcinoma. ScientificWorldJournal. 2013; 2013:479805. PMC: 3628498. DOI: 10.1155/2013/479805. View

Lena A, Shalom-Feuerstein R, Rivetti di Val Cervo P, Aberdam D, Knight R, Melino G . miR-203 represses 'stemness' by repressing DeltaNp63. Cell Death Differ. 2008; 15(7):1187-95. DOI: 10.1038/cdd.2008.69. View

Qi W, Liang W, Jiang H, Miuyee Waye M . The function of miRNA in hepatic cancer stem cell. Biomed Res Int. 2014; 2013:358902. PMC: 3870627. DOI: 10.1155/2013/358902. View

Chen G, Umelo I, Lv S, Teugels E, Fostier K, Kronenberger P . miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PLoS One. 2013; 8(3):e60317. PMC: 3608584. DOI: 10.1371/journal.pone.0060317. View

Phuah N, Hasima Nagoor N . Regulation of microRNAs by natural agents: new strategies in cancer therapies. Biomed Res Int. 2014; 2014:804510. PMC: 4165563. DOI: 10.1155/2014/804510. View

10.

Zhu X, Er K, Mao C, Yan Q, Xu H, Zhang Y . miR-203 suppresses tumor growth and angiogenesis by targeting VEGFA in cervical cancer. Cell Physiol Biochem. 2013; 32(1):64-73. DOI: 10.1159/000350125. View

11.

Dong S, Yang B, Guo H, Kang F . MicroRNAs regulate osteogenesis and chondrogenesis. Biochem Biophys Res Commun. 2012; 418(4):587-91. DOI: 10.1016/j.bbrc.2012.01.075. View

12.

Chen H, Han Z, Fan J, Xia J, Wu J, Qiu G . miR-203 expression predicts outcome after liver transplantation for hepatocellular carcinoma in cirrhotic liver. Med Oncol. 2011; 29(3):1859-65. DOI: 10.1007/s12032-011-0031-9. View

13.

Bueno M, Perez de Castro I, Gomez de Cedron M, Santos J, Calin G, Cigudosa J . Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008; 13(6):496-506. DOI: 10.1016/j.ccr.2008.04.018. View

14.

Ritchie W, Rasko J . Refining microRNA target predictions: sorting the wheat from the chaff. Biochem Biophys Res Commun. 2014; 445(4):780-4. DOI: 10.1016/j.bbrc.2014.01.181. View

15.

Furuta M, Kozaki K, Tanaka S, Arii S, Imoto I, Inazawa J . miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. 2009; 31(5):766-76. DOI: 10.1093/carcin/bgp250. View

16.

Vertemati M, Moscheni C, Petrella D, Lamperti L, Cossa M, Gambacorta M . Morphometric analysis of hepatocellular nodular lesions in HCV cirrhosis. Pathol Res Pract. 2012; 208(4):240-4. DOI: 10.1016/j.prp.2012.02.007. View

17.

Wei W, Wanjun L, Hui S, Dongyue C, Xinjun Y, Jisheng Z . miR-203 inhibits proliferation of HCC cells by targeting survivin. Cell Biochem Funct. 2012; 31(1):82-5. DOI: 10.1002/cbf.2863. View

18.

Fong Z, Tanabe K . The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review. Cancer. 2014; 120(18):2824-38. DOI: 10.1002/cncr.28730. View

19.

Dang Y, Luo D, Rong M, Chen G . Underexpression of miR-34a in hepatocellular carcinoma and its contribution towards enhancement of proliferating inhibitory effects of agents targeting c-MET. PLoS One. 2013; 8(4):e61054. PMC: 3622605. DOI: 10.1371/journal.pone.0061054. View

20.

Viticchie G, Lena A, Latina A, Formosa A, Gregersen L, Lund A . MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell Cycle. 2011; 10(7):1121-31. DOI: 10.4161/cc.10.7.15180. View