MicroRNA-492 expression promotes the progression of hepatic cancer by targeting PTEN

Abstract

BackgroundAberrant microRNA (miRNA) expression plays an essential role in the pathogenesis of Hepatocellular Carcinoma (HCC). However, specific involvement of miRNAs in HCC remains incompletely understood. The aim of this study was to explore the relevant microRNAs involved in the development of HCC.MethodsMicroRNA microarray was used to screen for the differentially expressed miRNAs in cancerous tissue and adjacent non-cancerous control tissue from patients with HCC (n = 3). Quantitative PCR was subsequently used to verify the results of microarray. Based on the findings, we investigated the role of miR-492 in the pathogenesis of HCC in vitro and in vivo using three tumor cells lines. Furthermore, we analyzed the clinical correlation of miR-492 expression with patient survival (n = 28).ResultsWe showed that microRNA-492 (miR-492) was elevated in HCC samples from patients with hepatic cancer. Knockdown of miR-492 attenuated the proliferation of cancer cell lines in vitro and inhibited primary tumor growth in vivo in SCID mice. We identified PTEN as a functional target for miR-492. Overexpression of miR-492 resulted in decreased PTEN expression and was associated with increased AKT activation in cancer cell lines. Moreover, miR-492-mediated increase of the proliferation of cancer cells was able to be suppressed by a PI3K inhibitor and an AKT inhibitor. The HCC patients with high miR-492/low PTEN had poorer survival.ConclusionsmiR-492 is implicated in the regulation of HCC progression through PTEN and AKT pathway. The data suggest that miR-492 is a biomarker of HCC and a potential therapeutic target for hepatocellular carcinoma.

MiR‐492 regulates metastatic properties of hepatoblastoma via CD44

“…Although deregulation in miRNA expression is a well‐known phenomenon in cancer and during metastasis, the functional role of single candidate miRNAs is still under investigation. Only few recent reports have shed light onto the functional role of miR‐492 in certain types of cancers . In this project, we investigated the functional impact of miR‐492 on HB metastasis in vitro and deciphered the genetic cascade triggered by the miRNA.…”

“…For breast and prostate cancer, similar effects on proliferation and anchorage‐independent growth have been published. Strong effects based on repressing miR‐492 by siRNA in liver cancer cell lines may depend on blocking miR‐492 in combination with its host gene KRT19 . In this regard, overexpression of miR‐492 may deliver more specific data.…”

“…Only few recent reports have shed light onto the functional role of miR-492 in certain types of cancers. 15,17,36 In this project, we investigated the functional impact of miR-492 on HB metastasis in vitro and deciphered the genetic cascade triggered by the miRNA. The results add to the understanding of its role in HB progression and indicate its diagnostic and prognostic relevance.…”

MicroRNA-301a promotes cell proliferation via PTEN targeting in Ewing's sarcoma cells

“…Numerous studies suggested that the transcriptional role of PTEN involves a key position in the complex network of tumor suppressor and oncogenes that regulate cellular transformation. PTEN downregulation was found in lung cancer (28), hepato cellular carcinoma (29), and prostate cancer (30). PTEN level might be related to the biology of Ewing's sarcoma cells and loss of PTEN could result in clinically more aggressive tumors (31).…”

Role of regulatory miRNAs of the PI3K/AKT/mTOR signaling in the pathogenesis of hepatocellular carcinoma

“…Molecular alteration Function Reference miR155-5p PTEN Upregulation Cellular proliferation and invasion (Fu et al, 2017) miR-494 PTEN Upregulation Cellular proliferation and invasion miR-519a PTEN Upregulation Cellular proliferation and invasion (Tu et al, 2016) miR-492 PTEN Upregulation Cellular proliferation and invasion (Jiang et al, 2014) miR-21 PTEN, hSulf-1 Upregulation Cellular proliferation and metastasis (Bao et al, 2013) miR-93 PTEN, CDKN1A Upregulation Cellular proliferation (Ohta et al, 2015) miR-222 PPP2R2A Upregulation Cellular proliferation (Wong et al, 2010) miR-3127 AKT, FOXO1 Upregulation Cellular proliferation Abbreviations: AKT, protein kinase B; miRNA, microRNA; mTOR, mammalian target of rapamycin; PI3K, phosphoinositide 3-kinase.…”