MicroRNA-148a suppresses epithelial-mesenchymal transition and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/β-catenin signaling pathway

Abstract

Epithelial-mesenchymal transition (EMT) plays a critical role in the process of cancer invasion and metastasis. The Wnt/β-catenin signaling pathway is known as a stimulative factor, which may trigger EMT and metastasis of cancer cells. In addition, several microRNAs (miRNAs) have been proven to regulate the EMT process. Recent research revealed that miR‑148a is downregulated in pancreatic cancer. However, the definite role of miR-148a in EMT and invasion of pancreatic cancer is still unknown. The present study attempted to demonstrate the underlying mechanism of miR-148a in the regulation of EMT and invasion of pancreatic cancer cells. Our data revealed that the expression of miR-148a was markedly downregulated in human pancreatic ductal adenocarcinoma (PDAC) cell lines and tissues. In addition, the downregulation of miR-148a was associated with poor prognosis and EMT phenotype. Furthermore, restoration of miR-148a expression inhibited the EMT process, as well as the migration and invasion of BxPC-3 pancreatic cancer cells. Wnt10b, a promoting molecule of the Wnt/β-catenin signaling pathway, was demonstrated by dual‑luciferase reporter assay to be a direct target of miR‑148a. Subsequently, we found that miR‑148a negatively regulated the protein expression of β-catenin, cyclin D1 and MMP-9, which were important components of the Wnt/β-catenin signaling pathway. In conclusion, these findings revealed that miR-148a suppresses EMT and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/β-catenin signaling pathway, and thus, miR-148a may serve as a novel therapeutic target for pancreatic cancer.

The interaction between miR‑148a and DNMT1 suppresses cell migration and invasion by reactivating tumor suppressor genes in pancreatic cancer

“…In addition, the downregulation of miR-148a is associated with poor prognosis and epithelial-mesenchymal transition (EMT). Conversely, restoration of miR-148a suppresses EMT and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/β-catenin signaling pathway (22). The present study aimed to reveal the interaction between miR-148a and DNMT1, and its effects on TSG expression, cell proliferation, migration and invasion of pancreatic cancer cells.…”

“…Dual luciferase reporter assay. A dual luciferase reporter assay was performed as previously described (22 Cell migration and invasion assays. The migratory and invasive abilities of AsPC-1 cells were examined using a Transwell chamber (Corning Incorporated, Corning, NY, USA).…”

Pancreatic cancer cell–derived exosomal microRNA‐27a promotes angiogenesis of human microvascular endothelial cells in pancreatic cancer via BTG2

“…8 miRs are a group of short non-coding RNA molecules with the length of 18-22 nucleotides, which regulate genes associated with cell apoptosis, differentiation and neoplastic transformation. 9 The abnormal expression of miRs has been implicated in the development and progression of a large array of cancers, including that of PC. 10 Additionally, the targeting of miR-27a by the anticancer agent 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) has been reported to diminish its expression leading to an inhibition of tumour cell growth through anti-angiogenic responses.…”

MicroRNA‐125b expression and intrahepatic metastasis are predictors for early recurrence after hepatocellular carcinoma resection

“…Thus, preoperative serum miR‐125b levels could serve as a useful biomarker to help reliably predict the presence of microvascular invasion before HCC patients undergo surgery . MicroRNA‐148a has been reported to inhibit the migration and invasion of ovarian cancer cells through targeting sphingosine‐1‐phosphate receptor 1 and to suppress epithelial–mesenchymal transition and invasion of pancreatic cancer cells by targeting Wnt10b and inhibiting the Wnt/β‐catenin signaling pathway …”