Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 3206 47

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.
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PMID:LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma. 3291 Jul 47