Long non-coding RNA SNHG10 upregulates BIN1 to suppress the tumorigenesis and epithelial–mesenchymal transition of epithelial ovarian cancer via sponging miR-200a-3p

Abstract

Epithelial ovarian cancer (EOC) is one of the most frequent and fatal gynecologic malignant tumors resulting in an unsatisfying prognosis. Long non-coding RNAs (lncRNAs) play pivotal roles in the tumorigenesis and progression of EOC. However, the profile of lncRNAs involved in EOC remains to be expanded to further improve clinical treatment strategy. In present study, we identified a novel tumor-suppressive lncRNA small nucleolar RNA host gene 10 (SNHG10) in EOC. Kaplan–Meier analysis and COX proportional hazard progression model showed that low expression of SNHG10 was correlated with a poor prognosis of EOC patients. Overexpressing SNHG10 suppressed the proliferation, colony formation, migration, and invasion of EOC cells. Furthermore, SNHG10 was predicted to sponge miR-200a-3p in EOC cells according to the LncBase v.2 experimental module. Then, the binding of SNHG10 and miR-200a-3p was confirmed by performing quantitative real-time PCR (qRT-PCR) and luciferase reporter assays. RNA immunoprecipitation (RIP) showed that SNHG10 and miR-200a-3p occupied the same Ago2 protein to form an RNA-induced silencing complex (RISC). By overlapping the results from the bioinformatics algorithms, tumor-suppressor bridging integrator-1 (BIN1) was found to be a main downstream target of the SNHG10/miR-200a-3p axis. Low expression of BIN1 in EOC tissues was detected by using immunohistochemistry (IHC). Besides, BIN1 and SNHG10 expression was positively correlated in EOC tissues. By performing miRNA rescue experiments, a SNHG10/miR-200a-3p/BIN1 axis and its promoting effects on malignant behaviors and epithelial–mesenchymal transition (EMT) process were verified in EOC cells. Moreover, SNHG10 overexpression significantly suppressed the tumorigenesis and EMT of EOC cells in vivo. Altogether, SNHG10 sponges miR-200a-3p to upregulate BIN1 and thereby exerting its tumor-suppressive effects in EOC. Therefore, the SNHG10/miR-200a-3p/BIN1 axis may act as a potential predictive biomarker and therapeutic target for treating EOC.

Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells

“…The expression of SNHG10, which was shown to suppress EMT in epithelial ovarian cancer [ 94 ], was reduced in the Tks4 KO cells, probably resulting in a pro-EMT effect.…”

Splicing factor SNRPA associated with microvascular invasion promotes hepatocellular carcinoma metastasis through activating NOTCH1/Snail pathway and is mediated by circSEC62/miR‐625‐5p axis

“…Mounting evidence has demonstrated that increased cancer cell invasion is associated with EMT-like process. [35][36][37][38] Interestingly, we found that overexpression of SNRPA promoted a transformation from the expression of epithelial markers to mesenchymal markers, indicating that SNRPA promoted the EMT-like process in HCC cells. Herein, we further explored the potential mechanism of SNRPA in the EMTlike process of HCC cells.…”

BMSC-Derived Exosomes Alleviate Sepsis-Associated Acute Respiratory Distress Syndrome by Activating the Nrf2 Pathway to Reverse Mitochondrial Dysfunction

“…Moreover, the increased expression of miR-200a-3p was inhibited by BMSC-exos (Supplementary Data, Figure S1), which may contribute to the underlying mechanism and still needs further research. Up to now, these studies found that circRNAs such as circSCMH1 [48], circBACH1 [49], and circST6GALNAC6 [50] and lncRNAs such as lncRNA Gpr137b [51], lncRNA MALAT1 [52], lncRNA SNHG10 [53], and lncRNA TUG1 [54] could reduce the miR-200a-3p expression. In our future research, we will conduct RNA sequencing of BMSC-exos and find which circRNAs or lncRNAs cause miR-200a-3p degradation.…”