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.

STAT1-induced upregulation of lncRNA RHPN1-AS1 predicts a poor prognosis of hepatocellular carcinoma and contributes to tumor progression via the miR-485/CDCA5 axis.

Long noncoding RNAs (lncRNAs) act as a critical regulator in tumor progression, but few lncRNAs have been functionally characterized in hepatocellular carcinoma (HCC). Using The Cancer Genome Atlas datasets and bioinformatic technology, we screened and identified a novel HCC-related lncRNA, RHPN1 antisense RNA 1 (RHPN1-AS1). We found that the levels of RHPN1-AS1 were distinctly upregulated in both HCC tissues and cell lines. RHPN1-AS1 was activated by the transcription factor STAT1. Clinical investigations suggested that higher levels of RHPN1-AS1 were distinctly correlated with histologic grade, advanced tumor, node, metastasis stage, and poorer clinical prognosis. Multivariate assays identified high RHPN1-AS1 expression as an unfavorable prognostic biomarker for patients with HCC. Functional study revealed that knockdown of RHPN1-AS1 was able to suppress cells proliferation and metastasis, and promote cell apoptosis. Further mechanistic investigation suggested that RHPN1-AS1 could promote CDCA5 expressions by functioning as a competing endogenous RNA for miR-485. This interaction resulted in consequentially suppression of HCC cells proliferation, migration, and invasion. Our findings for the first time illustrate how RHPN1-AS1 displayed its tumor-promotive roles in HCC and may offer a new biomarker and a potential therapeutic target for patients with HCC.

LncRNA RHPN1-AS1 accelerates proliferation, migration, and invasion via regulating miR-485-5p/BSG axis in hepatocellular carcinoma.

It is reported that long noncoding RNA RHPN1-AS1 (lncRNA RHPN1-AS1) functions as an oncogene among multiple types of cancers; however, the effect of lncRNA RHPN1-AS1 in hepatocellular carcinoma (HCC) is left to be investigated. The main purpose of this work was to study the effects of lncRNA RHPN1-AS1/miR-485-5p system on proliferation, migration, and invasion in HCC and future investigate the latent mechanisms. Our work found that lncRNA RHPN1-AS1 was observably up-regulated in HCC tissues and cell lines, especially HCCLM3 and SMMC-7721 cells. LncRNA RHPN1-AS1 knockdown decreased the capacity of proliferation, invasion, and migration in HCCLM3 and SMMC-7721 cells, which could be crippled by miR-485-5p inhibitor. Besides, the expression of basigin (BSG) was decreased after lncRNA RHPN1-AS1 silence, indicating the function of lncRNA RHPN1-AS1/miR-485-5p/BSG axis in HCC progression. Our study opens novel insights to help understand the mechanisms of lncRNA RHPN1-AS1/miR-485-5p/BSG axis in HCC progression, which may provide a new therapeutic target for HCC treatment.

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

Hepatocellular carcinoma (HCC) is a severe disease with high mortality in the world. Emerging evidence has suggested that lncRNAs play an important role in cancer progression, including HCC. This study aimed to comprehensively investigate the effect of lncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on HCC and its underlying molecular mechanism. In this study, we evaluated the expressions of lncRNA RHPN1-AS1 and miR-7-5p by qRT-RCR in both HCC tissue and HCC cells. Our findings showed that lncRNA RHPN1-AS1 was upregulated in HCC tissue and HCC cells, while miR-7-5p was downregulated. LncRNA RHPN1-AS1 expression in HCC patients was closely related to vascular invasion, tumor-node-metastasis (TNM) stage and barcelona clinic liver cancer (BCLC) stage. Furthermore, we quantified cell clone-formation ability, proliferation, migration and invasion of HCCLM3 and MHCC97 H cells using several assays (colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay and transwell assay, respectively). Functional experiments confirmed that silencing lncRNA RHPN1-AS1 inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97 H cells. After that, bioinformatics analysis, dual luciferase reporter gene assay, qRT-PCR and western blot were used to investigate the molecular mechanism of lncRNA RHPN1-AS1 on HCC. Mechanistically, the rescue experiments demonstrated that miR-7-5p inhibitor reversed the inhibition effect of silencing lncRNA RHPN1-AS1 on HCCLM3 cells proliferation, migration and invasion. Moreover, silencing lncRNA RHPN1-AS1 also inhibited the activation of PI3K/AKT/mTOR pathway. Taken together our findings demonstrated that lncRNA RHPN1-AS1 could facilitate cell proliferation, migration and invasion via targeting miR-7-5p and activating PI3K/AKT/mTOR pathway in HCC.

Silencing of the long non-coding RNA RHPN1-AS1 suppresses the epithelial-to-mesenchymal transition and inhibits breast cancer progression.

Breast cancer (BC) is a frequently diagnosed malignancy in women. Increasing evidence implicates mis-expression of the long non-coding RNA (lncRNA) RHPN1 antisense RNA 1 (RHPN1-AS1) in the development of multiple cancer types. However, little is known about the expression pattern and function of lncRNA RHPN1-AS1 in the pathobiology of BC. We evaluated the expression of RHPN1-AS1 in The Cancer Genome Atlas dataset, and analyzed associations between RHPN1-AS1 expression and clinicopathologic features of BC patients. Additionally, we compared the expression of RHPN1-AS1 between BC and breast non-tumor samples via quantitative real-time polymerase chain reaction, and in situ hybridization, and evaluated the prognostic value of RHPN1-AS1 in a BC tissue microarray. We examined the impact of RHPN1-AS1 knockdown on proliferation, migration, and invasion of BC cells in vitro, and tumor growth in vivo. Bioinformatics analyses were used to predict the function of RHPN1-AS1 in BC. RHPN1-AS1 expression was upregulated in BC and elevated RHPN1-AS1 expression was strongly associated with poor prognosis of BC patients. Moreover, both univariate and multivariate analyses revealed that RHPN1-AS1 was a significant and independent predictor of BC prognosis. Functionally, RHPN1-AS1 silencing attenuated BC cell proliferation, migration, and invasion in vitro, and reduced tumor growth in xenograft models. Furthermore, RHPN1-AS1 silencing was associated with a decrease in the expression of epithelial-to-mesenchymal transition (EMT) markers in the xenograft tumors, suggesting that RHPN1-AS1 promotes invasion in BC cells by enhancing EMT. These findings suggest that RHPN1-AS1 is a potential prognostic biomarker and therapeutic target for BC.

LncRNA RHPN1-AS1 promoted cell proliferation, invasion and migration in cervical cancer via the modulation of miR-299-3p/FGF2 axis.

AIMS: This study aims to determine the biological function and underlying mechanisms of lncRNA RHPN1 antisense RNA1 (RHPN1-AS1) in cervical cancer cell proliferation, invasion and migration. MAIN METHODS: Gene expression was analysed by quantitative real-time PCR; protein levels were determined by western blot assay; in vitro functional assays determined the cervical cancer cell progression; in vivo tumor growth of cervical cancer cell was determined in nude mice xenograft models. KEY FINDINGS: The results showed that RHPN1-AS1 was up-regulated in cervical cancer tissues and cell lines. In vitro functional assays demonstrated that RHPN1-AS1 overexpression promoted SiHa cell proliferation, invasion and migration; while RHPN1-AS1 knockdown showed the opposite effects. In vivo study showed that RHPN1-AS1 knockdown suppressed tumor growth in the nude mice. Further investigation showed that miR-299-3p was targeted and inversely regulated by RHPN1-AS1. In addition, miR-299-3p targeted the 3' untranslated region of fibroblast growth factor 2 (FGF2) to suppress its expression. The rescue experiments showed that the enhanced effects of RHPN1-AS1 overexpression on cell proliferation, growth, invasion and migration in SiHa cells were significantly attenuated by miR-299-3p overexpression or FGF2 inhibition. On the other hand, knockdown of miR-299-3p and overexpression of FGF2 both significantly increased cell proliferation, growth, invasion and migration in SiHa cells transfected with RHPN1-AS1 siRNA. SIGNIFICANCE: In conclusion, our results revealed that RHPN1-AS1 promoted cervical cancer progression via targeting miR-299-3p/FGF2 axis. Our data suggested that RHPN1-AS1/miR-299-3p/FGF2 axis may be a promising target for cervical cancer treatment.