LncRNA RHPN1-AS1 inhibition induces autophagy and apoptosis in prostate cancer cells via the miR-7-5p/EGFR/PI3K/AKT/mTOR signaling pathway.

LncRNA RHPN1-AS1 (RHPN1-AS1) has been confirmed to promote tumor progression in multiple cancers and is upregulated in prostate cancer (PCa), but whether it has an effect on PCa progression remains unclear. In this study, we found that PCa patients with high RHPN1-AS1 expression had a shorter survival time, and RHPN1-AS1 was significantly upregulated in PCa tissues and cells. Based on informatics analysis we predicted that miR-7-5p binds to 3'UTR of RHPN1-AS1 and epidermal growth factor receptor (EGFR) and verified it by luciferase reporter gene assay. Subsequently, we transfected PCa cells with RHPN1-AS1 overexpression vector (RHPN1-AS1), knockdown plasmids (sh-RHPN1-AS1) and/or miR-7-5p mimics or inhibitor and/or overexpression vector (EGFR) or small interfering RNA of EGFR (si-EGFR) or its control, and found that overexpression of RHPN1-AS1 inhibited miR-7-5p expression and promoted EGFR expression, silencing RHPN1-AS1 inhibited proliferation and invasion, and induced G2/M arrest, apoptosis and autophagy in PCa cells. 3MA (an inhibitor of autophagy)-mediated autophagy inhibition attenuated RHPN1-AS1 inhibition-induced apoptosis. Overexpression miR-7-5p or silencing EGFR promoted LC3-I to LC3-II conversion, enhanced autophagy activity, induced cleaved-caspase-3 expression and apoptosis in PCa cells. Furthermore, overexpression of RHPN1-AS1 promoted phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT and mTOR, inhibited LC3-I to LC3-II conversion and reduced apoptosis in PCa cells, while GSK2126458 (an inhibitor of PI3K) reversed the effect of RHPN1-AS1 on PCa cells. In summary, RHPN1-AS1 acted as a ceRNA of miR-7-5p to upregulate EGFR expression, silencing RHPN1-AS1 suppressed PCa tumor progression by inducing autophagy and apoptosis in PCa cells through the miR-7-5p/EGFR/PI3K/AKT/mTOR pathway.

Ma X ，Ren H ，Zhang Y ，Wang B ，Ma H ... -  《-》

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 ... -  《-》

Downregulation of lncRNA ZEB1-AS1 Represses Cell Proliferation, Migration, and Invasion Through Mediating PI3K/AKT/mTOR Signaling by miR-342-3p/CUL4B Axis in Prostate Cancer.

Ma T ，Chen H ，Wang P ，Yang N ，Bao J ... -  《-》

Muscleblind-like 1 antisense RNA 1 inhibits cell proliferation, invasion, and migration of prostate cancer by sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR signaling.

Ding X ，Xu X ，He XF ，Yuan Y ，Chen C ，Shen XY ，Su S ，Chen Z ，Xu ST ，Huang YH ... -  《-》

Long noncoding RNA OIP5-AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR-340-5p.

The abnormal expression of long noncoding RNAs (lncRNAs) plays an important role in the regulation of human cancer progression and drug resistance. The lncRNA OPI5-AS1 is a crucial regulator in some cancers; however, its role in cisplatin resistance of osteosarcoma remains unclear. We found that OIP5-AS1 was significantly upregulated in cisplatin-resistant (CR) osteosarcoma cells MG63-CR and SaOS2-CR compared with the corresponding parental cells. OIP5-AS1 silencing suppressed cell growth in vitro and in vivo, and promoted apoptosis of MG63-CR and SaOS2-CR cells, indicating that knockdown of OIP5-AS1 significantly decreased cisplatin resistance in MG63-CR and SaOS2-CR cells. This conclusion was supported by the decreased expression of the drug resistance-related factors multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein (P-gp) upon OIP5-AS1 silencing. In addition, OIP5-AS1 downregulation suppressed the PI3K/AKT/mTOR signaling pathway. Importantly, we demonstrated that OIP5-AS1 functions as a competing endogenous RNA of miR-340-5p and regulates the expression of lysophosphatidic acid acyltransferase (LPAATβ), which is a target of miR-340-5p. Moreover, downregulation of miR-340-5p partly reversed the inhibitory effect of OIP5-AS1 knockdown on the PI3K/AKT/mTOR pathway and therefore counteracted cisplatin resistance in MG63-CR and SaOS2-CR cells. In conclusion, OIP5-AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR-340-5p. Our results contribute to a better understanding of the function and mechanism of OIP5-AS1 in osteosarcoma cisplatin resistance.

Song L ，Zhou Z ，Gan Y ，Li P ，Xu Y ，Zhang Z ，Luo F ，Xu J ，Zhou Q ，Dai F ... -  《-》