miR-650 Promotes the Metastasis and Epithelial–Mesenchymal Transition of Hepatocellular Carcinoma by Directly Inhibiting LATS2 Expression

Abstract

Background/Aims: Previous studies have confirmed that microRNAs are involved in the metastasis and epithelial–mesenchymal transition (EMT) of malignancies. In this study, we examined whether miR-650 promotes the migration, invasion, and EMT of hepatocellular carcinoma (HCC) cells by targeting the large tumor suppressor kinase 2 gene (LATS2). Methods: qRT-PCR was used to detect expression of miR-650 in HCC tissues and paired normal tissues. MTT and Transwell assay were used to observe the effect of miR-650 on proliferation, migration and invasion of HCC cells. Western blot assay and Immunohistochemistry were performed to demonstrate association between miR-650 expression level and epithelial-mesenchymal transition (EMT) related protein. Mechanistically, Reporter luciferase assay was performed to reveal whether large tumor suppressor kinase 2 (LATS2) was a direct target of miR-650 in HCC cells. Results: We observed that miR-650 levels were largely up-regulated in HCC tissues, and that the increased expression was closely associated with the adverse clinical features of HCC patients. Additionally, the expression of LATS2, which was identified as a direct target of miR-650, can counteract the effects of miR-650 in HCC. Furthermore, we demonstrated that high miR-650 expression levels and low LATS2 expression levels in tumors may indicate a poor prognosis for HCC patients. Conclusion: In conclusion, the miR-650/LATS2 pathway may serve as a novel prognostic biomarker and an attractive therapeutic target for HCC patients.

<p>microRNA-944 inhibits the malignancy of hepatocellular carcinoma by directly targeting IGF-1R and deactivating the PI3K/Akt signaling pathway</p>

“…Increasing evidence indicates that a variety of miRNAs are aberrantly expressed in HCC. For example, miR-34a,9 miR-506,10 and miR-64511 are downregulated in HCC, whereas miR-197,12 miR-552,13 and miR-65014 are expressed at high levels in HCC. The dysregulated miRNAs exert their functions as oncogenes or tumor suppressors and play crucial roles in the initiation and progression of HCC 15–17.…”

Deregulation of miRNA in Helicobacter pylori-Induced Gastric MALT Lymphoma: From Mice to Human

“…We selected 9 of the 26 dysregulated miRNAs for validation by RT-qPCR. These were selected on the basis of the most significantly deregulation (highest fold-regulation values) in combination with the literature (identified miRNA targets, cancer types, predictive function): over-expressed miRNAs were miR-650 [20,21,22], miR196a-5p [23,24,25,26], miR-142-5p [10,11] and miR-138-5p [27] and downregulated miRNAs were miR-135a-5p [28,29,30], miR-7-5p [31,32,33], miR-210-3p [34,35,36], miR-153-3p [37,38,39] and miR-203a-3p [11,12]] (Table 1, miRNAs in bold text). Two miRNAs of the final list, miR-142 and miR-135, were already analyzed based on the d3Tx mouse model [14].…”

MiR‐222 inhibits apoptosis in porcine follicular granulosa cells by targeting the THBS1 gene

“…Porcine follicular granulosa cells (pGCs) are important in follicles, and apoptosis of pGCs is the main cause of follicular atresia. In cells, miRNAs regulate a variety of important physiological and pathological processes, including cell proliferation (Han, Yin, & Zhang, ), differentiation (Wu et al, ), apoptosis (Yao, Pan, Du, Zhang, & Li, ), and hormone biosynthesis and secretion (Song et al, ). Previous studies have indicated that miR‐222 is an important regulatory factor for cancer development (Galardi et al, ; Gong et al, ; Gu et al, ; Guo et al, ; Huang, Ouyang, Wei, & Yu, ; Iida et al, ; le Sage et al, ; Liu et al, ).…”