Abstract
SLC34A2 had been reported to be down-regulated in human NSCLC cells and patient tissues, and played a significant role in lung cancer. However, the mechanism of its unusual expressionin NSCLC has not been fully elucidated. In present study, we identified SLC34A2 was a direct target of miR-410 and could be inhibited by miR-410 transcriptionally and post-transcriptionally. MiR-410 promoted the growth, invasion and migration of NSCLC cells in vitro. An orthotopic xenograft nude mouse model further affirmed that miR-410 promoted NSCLC cell growth and metastasis in vivo. Moreover, restoring SLC34A2 expression effectively reversed the miR-410-mediated promotion of cell growth, invasion and migration in NSCLC cells. In addition, miR-410high /SLC34A2low expression signature frequently existed in NSCLC cells and tumor tissues. MiR-410 significantly increased the expression of DVL2 and β-catenin protein while decreased that of Gsk3β protein of Wnt/β-catenin signaling pathway, while SLC34A2 partly blocked the effects of miR-410 on those protein expressions. Hence, our data for the first time delineated that unusual expression of SLC34A2 was modulated by miR-410, and miR-410 might positivelycontribute to the tumorigenesis and development of NSCLC by down-regulating SLC34A2 and activating Wnt/β-catenin signaling pathway. MiR-410 might be a new potential therapeutic target for NSCLC.
Highlights
Lung cancer remains the world’s most significant reason of cancer death and the mortality rate is still increasing [1]
Since miR-410 was highly expressed in A549 cells, we further detected its expression in other non-small cell lung cancer (NSCLC) cell lines H1299 and 95D in which SLC34A2 was down-regulated compared with the normal cell line HBE
We found that miR-410 was significantly up-regulated and SLC34A2 was significantly down-regulated in 9 of 12 NSCLC tumor tissues compared with adjacent nontumorous tissues simultaneously by qRT-PCR (Figure 1D)
Summary
Lung cancer remains the world’s most significant reason of cancer death and the mortality rate is still increasing [1]. Increasing studies reported that AT-II cells might be transformed into cancer stem cells under exogenous or endogenous factors and induced carcinogenesis and development of NSCLC [11,12,13,14]. These indicated that SLC34A2 might function physiologically in AT-II and its mutations or abnormal expression was bound to affect the normal function of AT-II which was related to lung tumorigenesis. It is of great significance to reveal the molecular mechanism of abnormal expression of SLC34A2 for understanding the pathogenesis of NSCLC
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