Regulation of MET-mediated proliferation of thyroid carcinoma cells by miR-449b

Abstract

Thyroid carcinoma (TC) is a lethal cancer worldwide, whereas its carcinogenesis is not fully understood. Although growing evidence has demonstrated that dysregulation of microRNAs (miRNAs) contributes to the development of various cancers, the role of miRNAs in the pathogenesis of TC is poorly characterized. Here, we analyzed the levels of miR-449b in TC tissues and detected significantly lower miR-449b levels in TC tissues. Moreover, the low miR-449b levels were associated with poor survival. We then overexpressed miR-449b by miRNA mimic transfection and inhibited miR-449b by miRNA antisense transfection. Cell growth was analyzed by CCK-8 assay and MTT assay, and apoptosis and cell proliferation were analyzed by flow cytometry. Overexpression of miR-449b significantly inhibited cell growth, while depletion of miR-449b increased cell growth. Moreover, the effects of miR-449b on cell growth were through modulation of cell proliferation rather than through modulation of cell apoptosis. Targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay, showing that miR-449b binds to the 3'-UTR of MET (hepatocyte growth factor receptor) mRNA, to inhibit its expression in TC cells. MET levels were regulated by miR-449b in TT cells. Together, we show that reduced miR-449b levels in TT tissues may promote TC growth, through MET-mediated cell proliferation.

Long non-coding RNA GAS5 aggravates myocardial depression in mice with sepsis via the microRNA-449b/HMGB1 axis and the NF-κB signaling pathway

“…The interactions were further confirmed through RT-qPCR. miR-449b is an uncommonly investigated miRNA with its roles largely unrevealed except its inhibiting roles in several cancer types [38,39]. As partially coincident with our findings, miR-449b-5p has been documented to alleviate hepatocyte injury following liver ischemia and reperfusion via targeting HMGB1 [40], indicating its role in injury alleviation.…”

Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication

“…To the best of our knowledge there was no report showing adverse effects in the GLTP gene knock-in or -out animals. The GLTP expression was regulated by miR-449b, which is one of the isoforms of miR-449 and has its function related to cell cycle, differentiation and apoptosis 35 . Also important is the good safety of bicyclol in human at the dose used in the study.…”

Identification of novel diagnostic biomarkers for thyroid carcinoma

“…This is just the opposite in the “CancerG” level where one PCG was influenced by several lncRNAs, suggesting key roles of those 42 cancer PCGs in THCA (42 PCGs are listed in Supplementary Table 4 ). For example, ENSG00000105976 (c-Met) is an oncogene protein with tyrosine kinase activity, and its abnormal activation has been detected in various cancers, including THCA [ 36 , 37 ]. Another example is that ENSG00000066468 (FGFR-2), which has been implicated in the onset of THCA, was reduced in THCA [ 38 , 39 ].…”