miR-622 suppresses tumor formation by directly targeting VEGFA in papillary thyroid carcinoma

Abstract

BackgroundMicroRNAs (miRNAs) were reportedly to play crucial roles in papillary thyroid carcinoma (PTC) tumorigenesis and development. Therefore, the discovery of miRNAs may provide a new and powerful tool for diagnosis and treatment of PTC.PurposeThe aim of this study was to investigate the biological function and underlying mechanism of miR-622 in PTC.Materials and methodsThe expression levels of miR-622 in PTC patient tissues and cell lines were determined by quantitative RT-PCR (qRT-PCR). The biological function including cell proliferation, colony formation, migration and invasion, as well as underling mechanism of miR-622 in PTC, were also evaluated by a series of in vitro and in vivo experiments.ResultsmiR-622 expression level was significantly downregulated in PTC tissues and cell lines. Decreased miR-622 expression was associated with advanced clinical stage and lymph node metastasis (P<0.01). The overexpression of miR-622 in TPC-1 cells inhibited cell proliferation, migration and invasion in vitro, as well as suppress tumor growth in vivo. Moreover, we also demonstrated that miR-622 specifically targeted the 3′-UTR regions of vascular endothelial growth factor A (VEGFA) and inhibited its expression both mRNA level and protein levels. Overexpression of VEGFA reversed miR-622-mediated inhibition effect on cell proliferation, migration and invasion in thyroid cancer cells. More importantly, VEGFA expression was significantly increased and inversely correlated with the levels of miR-622 in PTC tissues.ConclusionThese results show that miR-622 acts as a tumor suppressor in thyroid cancer, at least in part, via targeting VEGFA, and suggest that miR-622 may serves as a potential target for treatment of thyroid cancer patients.

<p>MicroRNA-675 directly targets MAPK1 to suppress the oncogenicity of papillary thyroid cancer and is sponged by long non-coding RNA RMRP</p>

“…Recent studies have demonstrated that numerous miRNAs are dysregulated in PTC 36–39. The dysregulated miRNAs and their direct target genes consist of a complex network, which are implicated in the initiation and progression of PTC by regulating a range of biological processes 40–42.…”

miR-622 is a novel potential biomarker of breast carcinoma and impairs motility of breast cancer cells through targeting NUAK1 kinase

“…Increasing evidence suggests that miR-622 acts as a tumour suppressor in several types of human cancer such as glioma, 10 , 11 gastric, 12 , 13 pancreatic, 14 hepatocellular 15 thyroid 16 and oesophageal squamous cell carcinomas, 17 where it affects cell proliferation, migration and metastasis. Additionally, miR-622 suppresses migration and invasion of colorectal cancer cells by targeting K-RAS 18 and DYRK2.…”

Identification of novel targets of miR-622 in hepatocellular carcinoma reveals common regulation of cooperating genes and outlines the oncogenic role of zinc finger CCHC-type containing 11

“…Hypoxia and neovascularization are major pathological mechanisms in HCC driving progression and therapy resistance [51] , [52] , [53] , [54] , and current first-line therapeutic concepts in HCC (sorafenib, lenvatinib, bevacizumab) majorly target the hypoxia-associated VEGF-tumor-vascularization-axis [ 53 , 55 ]. Moreover, miR-622 was directly linked with hypoxia, VEGF-signaling and (neo-)vascularization in several cancer types including colorectal cancer [ 42 , 56 , 57 ]. In this regard, we found that the novel and yet undescribed target gene of miR-622 in liver cancer, ZCCHC11, was strongly correlated with hypoxia inducible factor 1, angiopoietin 2 and VEGFA in human HCC tissues.…”