<p>Effects of miR-330-3p on Invasion, Migration and EMT of Gastric Cancer Cells by Targeting PRRX1-Mediated Wnt/β-Catenin Signaling Pathway</p>

Abstract

Background: miRNA, as a biological marker, had more and more attention in recent years due to the important role it plays in cancer. Currently, there are extensive studies on miRNAs, among which miR-330-3p is reported to be implicated in the pathophysiological processes of various cancers. However, little progress has been made in the mechanism of miR-330-3p in gastric cancer. Objective: To explore the expression and relevant mechanism of miR-330-3p and PRRX1 in gastric cancer (GC). Methods: Forty-five GC patients (study group), from whom paired GC and paracancerous tissues were collected, and another 45 healthy subjects (control group) who underwent physical examination during the same period were enrolled. In addition, GC cells and human gastric mucosa cells were purchased, and miR-330-3p-mimics, miR-330-3pinhibitor, miR-NC, si-PRRX1, and sh-PRRX1 were transfected into MKN45, SGC7901 cell. QRT-PCR was employed to assess the miR-330-3p and PRRX1 expressions in the samples, and the cell expressions of PRRX1, GSK-3β, p-GSK-3β, β-catenin, p-β-catenin, cyclin D1, N-cadherin, E-cadherin and vimentin were evaluated by Western blot (WB). MTT, Transwell and wound-healing experiments were adopted to detect cell proliferation, invasion and migration. Results: MiR-330-3p was under-expressed, while PRRX1 was highly expressed in the serum of patients, both of which had an area under the curve (AUC) of more than 0.9. MiR-330-3p and PRRX1 were associated with tumor diameter, TNM staging, lymph node metastasis and differentiation of GC patients. Overexpression of miR-330-3p and inhibition of PRRX1 expression could suppress epithelial-mesenchymal transition (EMT), proliferation, invasion and apoptosis of cells. What is more, WB assay showed that overexpressed miR-330-3p and inhibited PRRX1 could inhibit the expression levels of p-GSK-3β, β-catenin, cyclin D1, N-cadherin and vimentin proteins, while elevating GSK-3β, p-β-catenin and E-cadherin protein expressions. Dual-luciferase reporter assay confirmed that there was a targeting relation between miR-330-3p and PRRX1. Furthermore, rescue experiments revealed that the cell proliferation, invasion, migration did not differ significantly between co-transfected miR-330-3p-mimics+sh-PRRX1, miR-330-3p-inhibitor+si-PRRX1 groups of MKN45 and SGC7901 and the miR-NC group (without transfected sequences). Conclusion: Overexpressed miR-330-3p can promote cell EMT, proliferation, invasion and apoptosis through inhibiting PRRX1-mediated Wnt/β-catenin signaling pathway, which is expected to be a potential therapeutic target for GC.

miR‐149 Suppresses the Proliferation and Metastasis of Human Gastric Cancer Cells by Targeting FOXC1

“…The occurrence of gastric cancer is a multistage and multifactorial pathological process involving gene mutations, epigenetic changes, and abnormal molecular signaling pathways [16]. miRNAs affect the stability and translation of target mRNAs and regulate processes such as cell cycle [17], proliferation [18], apoptosis [19], migration [20], and invasion [21]. Recently, numerous studies have shown that abnormal expression of miRNAs is closely related to the occurrence, development, and metastasis of gastric cancer.…”

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers

“…GC tissue samples [29] miR-330-3p Lymph node metastasis (p < 0.001). Serum, GC tissue samples [87] miR-361-5p…”

Circ_0058063 promotes progression of thyroid cancer by sponging miR-330-3p/SDC4 axis

“…To further explore the molecular mechanism circ_0058063 mediated, we performed bioinformatics analysis and found miR-330-3p might be the target of circ_0058063. Previously, a crucial tumor suppressor of miR-330-3p was observed in many malignant tumors [11–13]. In this study, we explored the roles of cytoplasmic circ_0058063 in TC in vitro and in vivo .…”