miRNA-148a serves as a prognostic factor and suppresses migration and invasion through Wnt1 in non-small cell lung cancer

Abstract

Lung cancer is the leading cause of cancer death in the world, and aberrant expression of miRNA is a common feature during the cancer initiation and development. Our previous study showed that levels of miRNA-148a assessed by quantitative real-time polymerase chain reaction (qRT-PCR) were a good prognosis factor for non-small cell lung cancer (NSCLC) patients. In this study, we used high-throughput formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays and in situ hybridization (ISH) to determine the clinical significances of miRNA-148a and aimed to find novel target of miRNA-148a in lung cancer. Our results showed that there were 86 of 159 patients with low miRNA-148a expression and miRNA-148a was significantly down-regulated in primary cancer tissues when compared with their adjacent normal lung tissues. Low expression of miRNA-148a was strongly associated with high tumor grade, lymph node (LN) metastasis and a higher risk of tumor-related death in NSCLC. Lentivirus mediated overexpression of miRNA-148a inhibited migration and invasion of A549 and H1299 lung cancer cells. Furthermore, we validated Wnt1 as a direct target of miRNA-148a. Our data showed that the Wnt1 expression was negatively correlated with the expression of miRNA-148a in both primary cancer tissues and their corresponding adjacent normal lung tissues. In addition, overexpression of miRNA-148a inhibited Wnt1 protein expression in cancer cells. And knocking down of Wnt-1 by siRNA had the similar effect of miRNA-148a overexpression on cell migration and invasion in lung cancer cells. In conclusion, our results suggest that miRNA-148a inhibited cell migration and invasion through targeting Wnt1 and this might provide a new insight into the molecular mechanisms of lung cancer metastasis.

Upregulation of circ_001569 predicts poor prognosis and promotes cell proliferation in non‑small cell lung cancer by regulating the Wnt/β‑catenin pathway

“…Reduced circ_001569 expression inhibits the Wnt/β-catenin pathway in NSCLC cells. The Wnt/β-catenin pathway is associated with cell proliferation and invasion in NSCLC; miRNA-148a serves as a prognostic factor, and suppresses cell migration and invasion through WNT1 in NSCLC (12). The association between circ_001569 expression and the Wnt/β-catenin pathway in NSCLC was additionally examined.…”

MicroRNA-374a Expression as a Prognostic Biomarker in Lung Adenocarcinoma

“…Zheng et al 22 reported that NSCLC patients with low miR-195 expression showed poor overall survival. In the study of Chen et al, 23 low miRNA-148a expression was significantly correlated with high histologic grade, frequent lymph node metastasis, and a poor OS in NSCLC. Further, miR-21, as an oncogenic miRNA, has been reported as a biomarker for predicting recur- rence, metastasis, and resistance of radiation and chemotherapy in NSCLC.…”

microRNA‐100 functions as a tumor suppressor in non‐small cell lung cancer via regulating epithelial‐mesenchymal transition and Wnt/β‐catenin by targeting HOXA1

“…Many upregulated miRNAs such as miR‐1269a, miR‐146, and miR‐378 have been reported to promote NSCLC cells . In contrast, some downregulated miRNAs such as miR‐148a, miR‐200c, and miR‐204 have been reported to repress NSCLC development . Thorough understanding of the association between abnormally expressed miRNAs and NSCLC development may therefore help to identify novel diagnostic and therapeutic biomarkers for the treatment of NSCLC.…”