MicroRNA-148a regulates the MAPK/ERK signaling pathway and suppresses the development of esophagus squamous cell carcinoma via targeting MAP3K9.

OBJECTIVE: Esophagus squamous cell carcinoma (ESCC) was a dominant histological type of esophagus cancer, which has a very high incidence due to distant metastasis and local invasion. MicroRNA-148a (miR-148a) functioned as a tumor suppressor in a variety of cancers. The purpose of our study was to explore the vital role of miR-148a in esophagus squamous cell carcinoma. PATIENTS AND METHODS: The Kaplan-Meier method was applied to calculate the 5-year overall survival of esophagus squamous cell carcinoma patients. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot were conducted to calculate the mRNA levels of miR-148a and genes. The cell counting kit-8 (CCK-8) and transwell assays were performed to measure the proliferative and invasive ability.
RESULTS: MiR-148a was observed to be significantly downregulated and the downregulation of miR-148 predicted poor prognosis of esophagus squamous cell carcinoma patients. MAP3K9 was a target gene of miR-148a and its expression was mediated by miR-148a through directly binding to the 3'-untranslated region (3'-UTR) of its mRNA in the esophagus squamous cell carcinoma. Moreover, miR-148a remarkably inhibited the proliferation and invasion through directly targeting to MAP3K9 via extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and epithelial-mesenchymal transition (EMT) in the ESCC cells. In addition, overexpression of miR-148a inhibited the growth of ESCC in vivo.
CONCLUSIONS: MiR-148a inhibited the proliferation and invasion through directly targeting to MAP3K9 by ERK/MAPK pathway and EMT in ESCC cells. The newly identified miR-148a/MAP3K9 axis provides a novel insight into the pathogenesis of the esophagus squamous cell carcinoma.