Long noncoding RNA PICSAR/miR-588/EIF6 axis regulates tumorigenesis of hepatocellular carcinoma by activating PI3K/AKT/mTOR signaling pathway.

Accumulating evidence has identified long noncoding RNAs (lncRNAs) as regulators in tumor progression and development. Here, we elucidated the function and possible molecular mechanisms of the effect of lncRNA-PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA) on the biological behaviors of HCC. In the present study, we found that PICSAR was upregulated in HCC tissues and cells and correlated with progression and poor prognosis in HCC patients. Gain- and loss-of-function experiments indicated that PICSAR enhanced cell proliferation, colony formation, and cell cycle progression and inhibited apoptosis of HCC cells. PICSAR could function as a competing endogenous RNA by sponging microRNA (miR)-588 in HCC cells. Mechanically, miR-588 inhibited HCC progression and alternation of miR-588 reversed the promotive effects of PICSAR on HCC cells. In addition, we confirmed that eukaryotic initiation factor 6 (EIF6) was a direct target of miR-588 in HCC and mediated the biological effects of miR-588 and PICSAR in HCC, resulting in PI3K/AKT/mTOR pathway activation. Our data identified PICSAR as a novel oncogenic lncRNA associated with malignant clinical outcomes in HCC patients. PICSAR played an oncogenic role by targeting miR-588 and subsequently promoted EIF6 expression and PI3K/AKT/mTOR activation in HCC. Our results revealed that PICSAR could be a potential prognostic biomarker and therapeutic target for HCC.

Liu Z ，Mo H ，Sun L ，Wang L ，Chen T ，Yao B ，Liu R ，Niu Y ，Tu K ，Xu Q ，Yang N ... -  《-》

microRNA-1914, which is regulated by lncRNA DUXAP10, inhibits cell proliferation by targeting the GPR39-mediated PI3K/AKT/mTOR pathway in HCC.

Increasing studies have confirmed that abnormally expressed microRNAs (miRNAs) take part in the carcinogenesis as well as the aggravation of hepatocellular carcinoma (HCC). However, little information is currently available about miR-1914 in HCC. Here, we first confirmed that miR-1914 inhibition in HCC cell lines and tumour specimens correlates with tumour size and histological grade. In a series of functional experiments, miR-1914 inhibited tumour proliferation and colony formation, resulting in cell cycle arrest and increased apoptosis. Moreover, miR-1914 mediated its functional effects by directly targeting GPR39 in HCC cells, leading to PI3K/AKT/mTOR repression. Restoring GPR39 expression incompletely counteracted the physiological roles of miR-1914 in HCC cells. In addition, down-regulation of AKT phosphorylation inhibited the effects of miR-1914 in HCC. Furthermore, the overexpression of lncRNA DUXAP10 negatively correlated with the expression of miR-1914 in HCC; thus, lncRNA DUXAP10 regulated miR-1914 expression and modulated the GPR39/PI3K/AKT-mediated cellular behaviours. In summary, the present study demonstrated for the first time that lncRNA DUXAP10-regulated miR-1914 plays a functional role in inhibiting HCC progression by targeting GPR39-mediated PI3K/AKT/mTOR pathway, and this miRNA represents a novel therapeutic target for patients with HCC.

Sun L ，Wang L ，Chen T ，Yao B ，Wang Y ，Li Q ，Yang W ，Liu Z ... -  《-》

Long non-coding RNA AGAP2-AS1, functioning as a competitive endogenous RNA, upregulates ANXA11 expression by sponging miR-16-5p and promotes proliferation and metastasis in hepatocellular carcinoma.

Liu Z ，Wang Y ，Wang L ，Yao B ，Sun L ，Liu R ，Chen T ，Niu Y ，Tu K ，Liu Q ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma.

Song XZ ，Ren XN ，Xu XJ ，Ruan XX ，Wang YL ，Yao TT ... -  《-》

MicroRNA-1468 promotes tumor progression by activating PPAR-γ-mediated AKT signaling in human hepatocellular carcinoma.

Liu Z ，Wang Y ，Dou C ，Sun L ，Li Q ，Wang L ，Xu Q ，Yang W ，Liu Q ，Tu K ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》