Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid Carcinoma

Abstract

BackgroundThe objective of this study was to explore the role of miR-199a-5p in the development of thyroid cancer, including its anti-proliferation effect and downstream signaling pathway.Material/MethodsWe conducted qRT-PCR analysis to detect the expressions of several microRNAs in 42 follicular thyroid carcinoma patients and 42 controls. We identified CTGF as target of miR-491, and viability and cell cycle status were determined in FTC-133 cells transfected with CTGF siRNA, miR-199a mimics, or inhibitors.ResultsWe identified an underexpression of miR-199a-5p in follicular thyroid carcinoma tissue samples compared with controls. Then we confirmed CTGF as a target of miR-199a-5p thyroid cells by using informatics analysis and luciferase reporter assay. Additionally, we found that mRNA and protein expression levels of CTGF were both clearly higher in malignant tissues than in benign tissues. miR-199a-5p mimics and CTGF siRNA similarly downregulated the expression of CTGF, and reduced the viability of FTC-133 cells by arresting the cell cycle in G0 phase. Transfection of miR-199a-5p inhibitors increased the expression of CTGF and promoted the viability of the cells by increasing the fraction of cells in G2/M and S phases.ConclusionsOur study proves that the CTGF gene is a target of miR-199a-5p, demonstrating the negatively related association between CTGF and miR-199a. These findings suggest that miR-199a-5p might be a novel therapeutic target in the treatment of follicular thyroid carcinoma.

Fibrogenic Signaling Is Suppressed in Hepatic Stellate Cells through Targeting of Connective Tissue Growth Factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p

“…Our data are supported by the decreased expression of miR-199a-5p in keloid tissue compared with normal human skin 46 and the very recent finding that miR-199a-5p functions as a tumor suppressor in follicular cancer by suppressing CCN2. 47 Furthermore, the concomitant inhibition of expression of a-SMA and/or collagen 1(a1) is consistent with their CCN2 dependency in HSCs 33 but may also result from the regulation of other miR-199a-5p targets. Although our mechanistic data are consistent with decreased miR-199a-5p accounting for increased CCN2 expression during HSC activation, other studies have found miR-199a-5p expression to be increased in fibrotic livers or in activated HSCs.…”

Up‐regulation of microRNA‐491‐5p suppresses cell proliferation and promotes apoptosis by targeting FOXP4 in human osteosarcoma

“…What's more, miR‐491 targets G‐protein‐coupled receptor kinase‐interacting protein 1 (GIT‐1), which blocked the activation of NF‐κB to attenuate cancer stem cell‐like properties of hepatocellular carcinoma . Besides, miR‐491 can also regulate its target genes, such as IGF2BP1, CTGF, TPX and Notch, functioning as tumour suppressor. Our study showed miR‐491‐5p suppressed the proliferation of human osteosarcoma cells and increased the cell apoptosis in vitro by targeting FOXP4 .…”

Identification of potential pathogenic candidates or diagnostic biomarkers in papillary thyroid carcinoma using expression and methylation profiles

“…A recent study revealed that hsa-miR-199a-5p expression was significantly downregulated in PTC tissues and cells, and it inhibited the progression of PTC by downregulating snail family transcriptional repressor 1 (SNAI1) (23). A previous study demonstrated that hsa-miR-199a-5p was downregulated in tumor tissues obtained from patients with follicular thyroid carcinoma (FTC), and exhibited a negative association with its target, connective tissue growth factor (24). Therefore, hsa-miR-199a-5p may serve as a novel biomarker for the clinical management of thyroid carcinoma.…”