MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway

Abstract

BackgroundIncreasing evidences demonstrate that miRNAs contribute to development and progression of hepatocellular carcinoma (HCC). Underexpression of miR-1296 is recently reported to promote growth and metastasis of human cancers. However, the expression and role of miR-1296 in HCC remain unknown.MethodsThe levels of miR-1296 in HCC tissues and cells were detected by qRT-PCR. Immunoblotting and immunofluorescence were used for detection of epithelial-to-mesenchymal transition (EMT) progression in HCC cells. Transwell assays were performed to determine migration and invasion of HCC cells. A lung metastasis mouse model was used to evaluated metastasis of HCC in vivo. The putative targets of miR-1296 were disclosed by public databases and a dual-luciferase reporter assay.ResultsWe found that the expression of miR-1296 was reduced in HCC tissues and cell lines, and it was associated with metastasis and recurrence of HCC. Notably, miR-1296 overexpression inhibited migration, invasion and EMT progress of HCCLM3 cells, while miR-1296 loss facilitated these biological behaviors of Hep3B cells in vitro and in vivo. In addition, miR-1296 inversely regulated SRPK1 abundance by directly binding to its 3′-UTR, which subsequently resulted in suppression of p-AKT. Either SRPK1 re-expression or PI3K/AKT pathway activation, at least partially, abolished the effects of miR-1296 on migration, invasion and EMT progress of HCC cells. Furthermore, miR-1296 and SRPK1 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the underexpression of miR-1296 in HCC. And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-1296.ConclusionsUnderexpression of miR-1296 potentially serves as a prognostic biomarker in HCC. Hypoxia-induced miR-1296 loss promotes metastasis and EMT of HCC cells probably by targeting SRPK1/AKT pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0675-y) contains supplementary material, which is available to authorized users.

LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa‐mir‐22‐3p

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MicroRNA‐301b‐3p contributes to tumour growth of human hepatocellular carcinoma by repressing vestigial like family member 4

“…Our previous studies have suggested that miRNAs are critical drivers or suppressors for the development and progression of HCC . For example, miR‐194‐5p functions as a tumour suppressor through inhibiting the tumour growth of HCC by targeting forkhead box A1 .…”

“…Accumulating studies have found that miRNAs are aberrantly expressed and dysfunctional in HCC . Recently, miRNAs have been shown to be associated with diagnosis, development, progression and prognosis of human HCC . miR‐301b‐3p is recently recognized as a cancer‐related miRNA.…”

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

“…MiR‐944 inhibited EMT and the metastasis of gastric cancer by the metastasis‐associated in colon cancer 1 (MACC1)/Met/Akt signaling pathway . MiR‐1296 inhibited EMT and the metastasis of hepatocellular carcinoma via the serine/threonine‐protein kinase 1/PI3K/Akt signaling pathway . Taken together, these data suggest that Akt plays a key role in EMT cellular signal transduction and that targeting Akt might be an effective approach to treat fibrosis and tumors (Table ).…”