<p>miR-939-5p Contributes to the Migration and Invasion of Pancreatic Cancer by Targeting ARHGAP4</p>

Abstract

Rho GTPase-activating protein 4 (ARHGAP4) is a GTPase-activating protein for the small GTPases of the Rho family that is involved in tumorigenesis. We recently reported that ARHGAP4 can mediate Warburg effect and malignant phenotype of pancreatic cancer. However, the regulation of ARHGAP4 remains unclear. Methods: ARHGAP4 and miR-939-5p expressions in pancreatic cancer tissues and cell lines were measured by real-time PCR or Western blotting. Pancreatic cancer cells were transfected with miR-939-5p inhibitor, miR-939-5p mimic and/or lentivirus expressing ARHGAP4, and the cell viability, invasion and migration were measured by CCK-8 and Transwell assay, respectively. The suppression of ARHGAP4 expression by miR-939-5p was revealed by luciferase reporter assay, real-time PCR or Western blotting. Results: ARHGAP4 expression was decreased, while miR-939-5p was increased in pancreatic cancer tissues compared with adjacent-normal pancreatic tissues. Higher miR-939-5p expression was correlated with advanced pathological stages and poor prognosis of pancreatic cancer patients. miR-939-5p directly targeted ARHGAP4. Either miR-939-5p down-regulation or ARHGAP4 overexpression inhibited viability, invasion and migration of pancreatic cancer cells. However, ARHGAP4 overexpression markedly inhibited the increased viability, migration, and invasion induced by miR-939-5p up-regulation in pancreatic cancer cells. Conclusion: These observations suggested that miR-939-5p regulates the malignant phenotype of pancreatic cancer cells by targeting ARHGAP4, establishing miR-939-5p as a novel regulator of ARHGAP4 with a critical role in tumorigenesis in pancreatic cancer.

ARHGAP4-SEPT2-SEPT9 complex enables both up- and down-modulation of integrin-mediated focal adhesions, cell migration, and invasion

“…While cell biological studies on the function of ARHGAP4 were rather limited in number, there has been a significant increase of them in recent years. To date, almost all fundamental researches of ARHGAP4 have reported prominent functions in inhibiting cell migration and invasion (Shen et al, 2020;Vogt et al, 2007). Meanwhile, our study must be the first to our knowledge that revealed its molecular mechanism dominated by the SEPT2/9-driven modulation of FAs via its Rho-GAP and SH3 domains.…”

Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study

“…hsa-miR-939-5p, of potential interest for its role in invasive cancer, is reportedly upregulated in lung adenocarcinomas [43], hepatocellular carcinomas [44,45], ovarian cancer tissue [46] and in the promotion of blood vessel invasion in breast cancer [47]. The recent study by Shen et al [48] shed some light on the role of this hsa-miR-939-5p in PDAC biology and prognosis. By studying human pancreatic cancer tissues and cell lines, the authors demonstrated that high expression levels of this miRNA are associated with a poor prognosis in patients, while promoting in vitro tumor cell migration and invasion by targeting the Rho GTPase, activating protein 4.…”

Identification of Circulating Serum miRNAs as Novel Biomarkers in Pancreatic Cancer Using a Penalized Algorithm

“…Among the 39 PC-specific markers, 15 miRNAs have been reported to serve as PC markers in previous studies. Some of these (miR-155-5p, miR-939-5p, miR-346, miR-3064-5p, miR-661, miR-26a-5p, miR-200b-5p, and miR-218-5p) were found to be differentially expressed in PC tissues [15][16][17][18][19][20]23,24,27,[30][31][32]34,35,[37][38][39]. miR-939-5p, miR-200b-5p, and miR-218-5p were also differentially expressed in PC cell lines.…”