miR-369 inhibits Liver Cancer progression by targeting ZEB1 pathway and predicts the prognosis of HCC patients

Abstract

Increasing evidences show that microRNAs (miRNAs) are involved in the regulation of tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). miR-369 works as a tumor suppressor in both lung cancer and thyroid cancer. However, the potential biological function of miR-369 in HCC is unknown. Herein, we for first found that miR-369 expression was downregulated in HCC tissues and predicted the poor prognosis of HCC patients. Forced miR-369 expression inhibited the proliferation and metastasis of HCC cells in vitro and in vivo . Mechanically, bioinformatics and luciferase reporter analysis identified Zinc finger E-box binding homeobox 1 (ZEB1) as a direct target of miR-369 in HCC cells. miR-369 overexpressing downregulated the ZEB1 mRNA and protein expression in HCC cells. miR-369 expression was negatively associated with ZEB1 expression in human HCC tissues. More importantly, the ZEB1 siRNA diminished the discrepancy of growth and metastasis capacity between miR-369 overexpression HCC cells and control cells.

The potential of miR-153 as aggressive prostate cancer biomarker

“…Xie et al evidenced that miR-520a inhibits non-small cell lung cancer (NSCLC) progression through suppression of ribonucleoside-diphosphate reductase subunit M2 (RRM2) and Wnt signaling pathways [ 21 ]. Dong et al show that miR-369 expression is reduced in hepatocellular carcinoma (HCC) tissues [ 22 ].…”

Epigenetic Changes Affecting the Development of Hepatocellular Carcinoma

“…Cell apoptosis via antiapoptotic proteins (p53, bax, bcl-2, cyto C, and caspase 3), G1-phase cell cycle arrest via cell cycle regulators (cyclin D1 and CDK2/4/6) [26] Upregulated HDAC9 Epithelial-mesenchymal transition process activation; cellular stemness properties regulation [27] Non-coding RNAs miR-221/222 Enhanced cell growth via p27 regulation mTOR kinase regulation [28] miR-369 Zinc finger E-box binding homeobox 1 regulation [29] miR-3174 FOXO1 regulation [30] miR-383 IL-17 via STAT3 signaling pathway regulation [31] miR-361-5p CXCR6, VEGFA, or MAP3K9 regulation [32] miR-186 CSCs self-renewal [33] miR-186 Protein tyrosine phosphatase non-receptor type 11 regulation [34] miR-122 Tumor growth regulation [35] HOTAIR Proliferation, regulation of pluripotency, metastasis, and sensitivity to chemotherapeutics [36] HOTTIP Survival, tumor grade, and prognosis [37] Table 1. Cont.…”

“…Additional functional studies on a mouse model of liver cancer demonstrated that miR-221 overexpression stimulated the growth of tumorigenic murine hepatic progenitor cells [28]. Another study showed that miR-369, which targets zinc finger E-box-binding homeobox 1, is downregulated in liver fibrosis and liver cancer tissues, and can predict a poor prognosis in HCC patients [29]. Additionally, when miR-369 expression was restored, proliferation and metastasis of HCC cells in vitro and in vivo were inhibited.…”

The Elevated Circ_0067835 Could Accelerate Cell Proliferation and Metastasis via miR‐1236‐3p/Twist2 Axis in Hepatocellular Carcinoma

“…Researches have revealed that circRNAs can regulate various cell biology through interacting with couples of microRNAs (miRNAs), that has been named as a competing endogenous RNA (ceRNA) mechanism [ 6 – 9 , 16 , 17 ]. miRNAs may regulate various functions through binding with the 3′ untranslated regions (UTR) of downstream target genes in HCC [ 18 – 21 ]. miR-1236-3p has been demonstrated to be involved with some digestive system cancers, such as gastric cancer [ 22 , 23 ] and colorectal cancer [ 24 ].…”