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.

Our previous research indicated miR-410 played a critical role in promoting the tumorigenesis and development of NSCLC (non-small cells lung cancer). MiR-410 has been recently reported to be crucial for development and differentiation of embryonic stem cells. But it remains elusive whether miR-410 stimulates the stemness of cancer until now. Herein, we identify miR-410 induces the stemness and is associated with the progression of NSCLC. We demonstrate miR-410 increases the levels of stem cells marker Sox2, Oct4, Nanog, CXCR4 as well as lung cancer stem cells surface marker CD44 and CD166. MiR-410 promotes stem cells-like properties such as proliferation, sphere formation, metastasis and chemoresistance. Moreover, Gsk3β is directly targeted and post-transcriptionally downregulated by miR-410. Also, the expression levels of miR-410 and Gsk3β may be correlated to clinicopathological differentiation in NSCLC tumor specimens. Additionally, we demonstrate miR-410 induces stemness through inhibiting Gsk3β but increasing Sox2, Oct4, Nanog and CXCR4, which binds to β-catenin signaling. In conclusion, our findings identify the miR-410/Gsk3β/β-catenin signaling axis is a novel molecular circuit in inducing stemness of NSCLC.

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Sharpbelly Hemiculter leucisculus (Basilewski, 1855) is a small, widespread, and native cyprinid fish with prominent habitat suitability and high invasive potential and is becoming the dominant species in freshwater ecosystems under intensified environmental disturbances. But how H. leucisculus acclimates to extremely heterogeneous environments remains unclear. In current study, the genetic structure of H. leucisculus was analyzed using Bayesian phylogenetic inference, haplotype network, and STRUCTURE base on cytb gene across 18 populations spanning 20 degrees of latitude and 18 degrees of longitude in China. The morphological diversification of body size and shape for H. leucisculus along the climate gradient was studied. The results showed that the 18 H. leucisculus populations were divided into 3 clusters: one cluster mainly from Huanghe River Basin, another cluster mainly from Yangzi River Basin, and H cluster containing Hainan and Beihai populations. The fish from southern populations were deeper bodied while individuals from northern populations were more slender. Inland individuals were more streamlined while coastal individuals were of deeper body. The partial Mantel test predicts that the potential mechanism underlining the intraspecies morphological diversification along climate gradients is primarily the divergent selection pressures among different environments, while genetic variation had less contribution to morphological differentiation. The formation of the Nanling Mountain Range could drive genetic differentiation between Beihai population and those from Yangzi River Basin. The present results highlight strong selective pressures of climate on widespread species and enrich morphological differentiation basis of acclimation for species with high habitat suitability and invasive potential.