Down-regulation of microRNA-125b-2-3p is a risk factor for a poor prognosis in hepatocellular carcinoma

Bioengineered. 2021 Dec;12(1):1627-1641. doi: 10.1080/21655979.2021.1921549.

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of mortality in cancer patients, but the association between miR-125b-2-3p and the onset and prognosis of HCC has not been reported in previous studies; thus, the clinicopathological implications of miR-125b-2-3p in HCC require elaboration. To examine the expression of miR-125b-2-3p in HCC, both in-house RT-qPCR and public datasets were used to calculate the standard mean difference (SMD) and the summary receiver operating characteristic (sROC). MiR-125b-2-3p was markedly lower in HCC than in non-tumor tissue as assessed by the in-house RT-qPCR which was confirmed by the integrative analysis showing the SMD being -0.69 and the area under the curve (AUC) being 0.84 based on 1,233 cases of HCC and 630 cases of non-HCC controls. To gain a overview of the clinical value of miR-125b-2-3p in HCC, all possible datasets were integrated, and lower miR-125b-2-3p levels could lead to poorer differentiation and a more advanced clinical stage of HCC. The hazard ratio (HR) of miR-125b-2-3p was also calculated using a Cox proportional hazards model, and the miR-125b-2-3p level could act as an protective indication for the survival with the HR being 0.74 based on 586 cases of HCC. Furthermore, the effect of nitidine chloride (NC), a natural bioactive phytochemical alkaloid, on the regulation of miR-125b-2-3p and its potential targets was also investigated. The miR-125b-2-3p level was increased after NC treatment, while the expression of its potential target PRKCA was reduced. Above all, a low-expressed level of miR-125b-2-3p plays a tumor suppressive role in HCC.

Keywords: RT-qPCR; hepatocellular carcinoma; miR-125b-3p; nitidine chloride; prognosis; standard mean difference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Down-Regulation / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Prognosis
  • ROC Curve
  • Risk Factors

Substances

  • MIRN125 microRNA, human
  • MicroRNAs

Grants and funding

This research was supported by National Natural Science Foundation of China (NSFC 81860717), Natural Science Foundation of Guangxi, China (2019GXNSFAA245074, 2017GXNSFAA198017), Guangxi Zhuang Autonomous Region Health Committee Self-Financed Scientific Research Project (Z20190529), Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University Training Program for Distinguished Young Scholars, Guangxi Medical High-level Key Talents Training ‘139’ Program (2020), Guangxi Educational Science Planning Key Project (2021B167), Guangxi Higher Education Undergraduate Teaching Reform Project (2020JGA146), Guangxi Medical University Education and Teaching Reform Project (2019XJGZ04), Guangxi Medical University Future Academic Star (WLXSZX19007), and Innovation and Entrepreneurship Project Of College Students (02610220016X);