MicroRNA-101 has a suppressive role in osteosarcoma cells through the targeting of c-FOS

Abstract

MicroRNAs (miRs) have been implicated in the development and progression of osteosarcoma (OS). However, the underlying mechanism of miR-101 in regulating of the proliferation, migration and invasion of OS cells remains to be elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction data revealed that miR-101 was frequently downregulated in the tissue samples of 12 patients with OS compared with their matched adjacent non-tumor tissues. Furthermore, miR-101 was significantly downregulated in three common OS cell lines, Saos-2, MG63 and U2OS, compared with the human osteoblast cell line, hFOB1.19 (P<0.01). A luciferase reporter assay was also performed and identified c-FOS as a novel target of miR-101 in U2OS cells; overexpression of miR-101 significantly suppressed the protein expression levels of c-FOS, while knockdown of miR-101 significantly enhanced the formers' expression levels in U2OS cells (P<0.01). Independent inhibition of c-FOS and overexpression of miR-101 expression levels significantly suppressed U2OS cell proliferation, migration and invasion (P<0.01). However, overexpression of c-FOS reversed the inhibitory effect of miR-101 upregulation on proliferation, migration and invasion of U2OS cells, suggesting that miR-101 acts as a tumor suppressor in OS cells via targeting of c-FOS. Thus, we propose that the miR-101/c-FOS axis may be a potential therapeutic target for OS.

MicroRNA-101 Inhibits Growth, Proliferation and Migration and Induces Apoptosis of Breast Cancer Cells by Targeting Sex-Determining Region Y-Box 2

“…As miRNAs usually exert their control by targeting downstream genes, the identification of miR-101 downstream target genes played an important role in understanding its potential mechanism. Previous studies have reported that miR-101 targets COX2, c-FOS, CXCR7, SOX9, EZH2 and Rac1 [11-14, 18, 19, 38]. …”

“…These results indicated that miR-101 plays key roles in BC progression. Although miR-101 has been reported to target many downstream genes, including CDK8 [10], c-FOS [11], CXCR7 [18], SOX9 [14, 19] and GSK3β [20], the potential correlation between miR-101 and Sex-determining region Y-box 2 (SOX2) in BC is still unknown and needs to be further explored.…”

“…Recent studies have demonstrated that miRNA dysregulation plays critical roles in carcinogenesis and the metastasis of many cancers, including BC [4-9]. More recently, microRNA-101 (miR-101) has been reported to be downregulated in carcinoma tissues compared with adjacent healthy tissues in many types of cancers, including laryngeal squamous cell carcinoma [10], osteosarcoma [11], glioma [12], papillary thyroid carcinoma [13], hepatocellular carcinoma [14] and gallbladder carcinoma [15], suggesting it functions as a tumor suppressor. A correlation between miR-101 expression and BC has also been reported.…”

Downregulation of microRNA-95-3p suppresses cell growth of osteosarcoma via CDKN1A/p21 expression

“…Unlike siRNAs, miRNAs have multiple target genes (15). As endogenous RNA interference is triggered, miRNAs regulate cells which are closer to a physiological level instead of regulation through a simple gene knockout (16). We found that downregulation of microRNA-95-3p expression suppresses cell growth, induced apoptosis, increased caspase-3 and caspase-9 activities and bax protein expression in osteosarcoma cells; overexpression of microRNA-95-3p increased cell growth, and inhibited apoptosis of osteosarcoma cells, suggesting that microRNA-95-3p has a potential benefit in osteosarcoma.…”

microRNA-101 Represents an Innovative Bio-Marker in Oral Cancer Detection

“…Currently, growing evidences have indicated that miRNAs could be employed as novel bio-markers for non-invasive detection of various diseases, especially tumors [7,8]. Among these miRNAs, miR-101 is identi ed as a tumor suppressor, and its abnormal expression was observed in a variety types of human tumor, such as heaptatocellular carcinoma, osteosarcoma, etc [9,10]. It was reported that miR-101 could inhibit tumor cell proliferation and invasive capacity, thus played an inhibitory role in development of cancer [11,12].…”