MiR-589-5p is a potential prognostic marker of hepatocellular carcinoma and regulates tumor cell growth by targeting MIG-6

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs approximately with 22 nucleotides. Accumulating evidence indicates that microRNAs are involved in carcinogenesis and tumor progression. Some recent investigations have also reported that several microRNAs could act as biomarkers in cancer diagnosis and prognosis. MicroRNA-589-5p (miR-589-5p) is a less studied microRNA, in this study, we explored its roles in hepatocellular carcinoma (HCC). We analyzed miR-589-5p expression in HCC tissues by sequencing data and proved the expression in liver cancer cell lines by quantitative real-time PCR (qRT-PCR). We studied the effect of miR-589-5p on the growth of liver cancer cells by MTT assay, colony formation and flow cytometry, and identified its target gene by luciferase reporter assay. We found that miR-589-5p was commonly overexpressed in HCC specimens. High expression of miR-589-5p was a risk factor for HCC patient (Hazard ratio [HR] = 1.434; 95% confidence intervals [CI] = 1.006-2.044; p = 0.046). We also found miR-589-5p had higher expression in hepatocarcinoma cell lines HepG2 and HuH-7 than did in normal hepatocyte Lo-2. We identified that suppression of miR-589-5p inhibited cell proliferation and cell cycle progression by loss-of-function studies. Furthermore, we found mitogen-inducible gene 6 (MIG-6) to be a target of miR-589-5p. Our study demonstrated that miR-589-5p facilitated the growth of liver cancer cells by targeting MIG-6 and could be a prognosis biomarker for HCC. Suppression of miR-589-5p may be a feasible approach for inhibiting HCC progress.

WITHDRAWN: Mig-6 Promotes the Apoptosis and Inhibits of the Flux of Autophagy in HCC Cell Lines Through Modulating Mig-6/miR-193a-3p/TGF-β2 Axis

“…As reported, Mig-6 could be regulated by certain miRNAs [20][21][22][23], Especially miR-589-5p and miR-374a, regulated the proliferation of HCC cells by targeting Mig-6 [24,25]. These studies stimulated the interest in exploring whether Mig-6 could affect the changes in miRNAs.…”

MicroRNA‑589 serves as a tumor suppressor microRNA through directly targeting metastasis‑associated protein 2 in breast cancer

“…As a novel cancer-associated miRNA, miR-589 serves as an oncogene in gastric cancer (15). However, miR-589 may act as a tumor suppressor in hepatocellular carcinoma, glioma and lung cancer (11–14). The role of miR-589 in TNBC has yet to be established.…”

“…In addition, the same miRNA may serve as different roles in different biological functions in the same cancer tissue. In hepatocellular carcinoma, miR-589 serves a contrary role in the progression of cancer cells, including inhibiting the proliferation of cancer cell proliferation and maintaining the stemness and enhancing the chemoresistance to doxorubicin (11,14,20). The same miRNA may regulate different genes in cancer, and the gene may be regulated by different miRNAs in different tissues.…”

“…The same miRNA may regulate different genes in cancer, and the gene may be regulated by different miRNAs in different tissues. Previous studies revealed that miR-589 could regulate many genes, including LIFR, zinc finger MYND-type containing 19, signal transducer and activator of transcription 3, HDAC5 and mitogen-activated protein kinase 8 (11–15,20). To explore the molecular mechanism of miR-589 in inhibiting TNBC progression, publicly available bioinformatic algorithms were used to analyze the target gene of miR-589.…”

“…Although the study of miRNAs is challenging due to the variable downstream target genes of miRNAs, the application of miRNAs for TNBC therapy is crucial. Previous studies illustrated that miRNA-589 (miR-589) serves as a tumor suppressor in non-small cell lung cancer, glioma and hepatocellular carcinoma (11–14). By contrast, miR-589 acts as an oncogene in gastric cancer (15).…”