No abstract

No abstract

In recent years, the insulin-like growth factor (IGF-1) and serine-arginine protein kinase 1 (SRPK1) have been reported to be implicated in the pithelial-mesenchymal transition (EMT) in many kinds of malignancies. However, the potential roles of IGF-1-SRPK1 signaling in the EMT of gastric cancer (GC) have not been investigated. In the present study, the in-vitro assays were used to investigate the molecular role of SRPK1 in cell cycle, motility and invasiveness. We demonstrated that the expressions of SRPK1 or insulin-like growth factor receptor 1 (IGF1R) were significantly increased in GC tissues and cells than those in normal tissues and GES-1 cells, and closely associated with metastasis, stage and prognosis. Western blot analysis showed that IGF-1 treatment can induce the expression of p-AKT and EMT biomarkers (N-cadherin, MMP2 and Slug) in a dose-dependent fashion in MGC803 and BGC823 cells. On the other hand, the knockdown of SRPK1 attenuated IGF-1-induced increase of EMT biomarkers and p-AKT. Besides, in-vitro analysis showed that knockdown of SRPK1 induced cell cycle arrest in G0/G1 phase, and affected cell migration and invasion. In conclusion, IGF-1-IGF1R pathway induced the expression of SRPK1 to control the progression of EMT via AKT pathway in the development of GC. Our findings lay a promising foundation for the IGF-1-IGF1R axis-targeting therapy in GC patients.

BackgroundMiR-216b has been reported to be involved in the development of some cancers, however, the role of miR-216b in colorectal cancer (CRC) remains unclear.PurposeThis study aimed to investigate the mechanism underlying miR-216b-induced CRC development.MethodsWe detected the expression of miR-216b in 80 cases of CRC tissues and cell lines, and further analyzed the association between miR-216b and clinical pathological indicators as well as prognosis. In vitro, the miR-216b overexpression cell model was established for further functional assay.ResultsWe demonstrated that miR-216b in CRC tissues and cell lines was markedly decreased compared with corresponding adjacent normal tissues and colonic mucosal epithelial cell line, and was obviously associated with the TNM stage, lymph node metastases, and poor overall survival as well as recurrence-free survival. Furthermore, we found that miR-216b inhibited cell proliferation, cell cycle, migration, and invasion by targeting 3′-UTR of SRPK1. Besides, SRPK1 over-expression reversed miR-216b-inhibited cell proliferation, migration and invasion, while SRPK1 inhibition aggravated these effects.ConclusionsWe identified that miR-216b suppresses colorectal cancer proliferation, migration and invasion by targeting SRPK1, which shed light on how miR-216b functions in CRC pathogenesis.

Background/aims: MiR-216b and forkhead box M1 (FOXM1) were demonstrated to exert their biological effects on the development and progression of tumors. This study aimed to investigate the expression and role of miR-216b and FOXM1 in tissues and cell lines of non-small cell lung cancer (NSCLC). Methods: The expressions of miR-216b and FOXM1 in NSCLC tissues and cells were detected by qRT-PCR and Western blot analysis. Cell proliferation was measured by CCK-8 assay. Cell migration and invasion were confirmed by Transwell assay. Finally, the bioinformatics and dual-luciferase reporter assay were conducted to validate the relationship of miR-216b and FOXM1. Results: Compared with normal tissues and cells, the expression of miR-216b was obviously decreased in NSCLC tissues and cells. However, the expressions of FOXM1 mRNA and protein were significantly increased, and negatively correlated with the expression of miR-216b. Multivariate Cox’s regression analysis suggested that miR-216b or FOXM1 expression was an independent prognostic factor for patients with NSCLC. MiR-216b overexpression remarkably repressed cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of NSCLC cells. The bioinformatics and dual-luciferase reporter assay validated that the 3ʹ-untranslated region (3ʹ-UTR) of FOXM1 mRNA was indeed a direct target of FOXM1. In vitro, overexpression of FOXM1 partially eliminated inhibitory effects of miR-216b on cell proliferation, migration, and invasion, whereas inhibition of FOXM1 contributed to inhibitory effects mediated by miR-216b. Conclusion: MiR-216b inhibits cell proliferation, migration, invasion, and EMT by targeting the expression of FOXM1 in human NSCLC. These findings suggested a potential therapeutic role of miR-216b in patients of NSCLC.