Dataset Information

Decreased long intergenic noncoding RNA P7 predicts unfavorable prognosis and promotes tumor proliferation via the modulation of the STAT1-MAPK pathway in hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is the most common neoplasm and is a leading cause of cancer-related death. Despite advances in the diagnosis and management of HCC, its prognosis remain unfavorable. Accumulating evidence has shown that long intergenic noncoding RNAs (lincRNAs) play central roles in the development of HCC. In this study, we identified a long intergenic noncoding RNA referred to as lincRNA P7 in HCC and explored its clinical significance and biological functions in HCC. The expression level of lincRNA P7 was significantly aberrantly deceased in HCC cancer tissues and cells lines. Gain- and loss-of-function experiments revealed that overexpression of lincRNA P7 significantly inhibited the proliferation of HCC-derived cancer cells, whereas lincRNA P7 knockdown promoted cell growth. Mechanistically, lincRNA P7 blocked Erk1/2 signaling and repressed activation of the STAT1 pathway. In nude mouse models, we show that overexpression of lincRNA P7 effectively repressed HCC xenograft tumor growth in vivo. Moreover, a clinical investigation demonstrated that down-regulated lincRNA P7 expression correlated with liver cirrhosis, Hepatitis B virus (HBV) infection, clinical stage of the tumor and recurrence. A Kaplan-Meier survival analysis showed that the expression of lincRNA P7 was significantly related to overall survival (P = 0.003) and recurrence-free survival (P = 0.031). Collectively, our findings suggested that the down-regulation of lincRNA P7 predicts poor clinical outcomes for HCC patients and might be a powerful candidate prognostic biomarker and target in HCC.

SUBMITTER: Cheng S

PROVIDER: S-EPMC6281420 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Decreased long intergenic noncoding RNA P7 predicts unfavorable prognosis and promotes tumor proliferation via the modulation of the STAT1-MAPK pathway in hepatocellular carcinoma.

Cheng Sijie S Li Tieling T Wang Cheng C Wang Keyu K Lai Chengcai C Yan Jin J Fan Hongxia H Sun Fang F Wang Zhaohai Z Zhang Peirui P Yu Linxiang L Hong Zhixian Z Lei Guanglin G Sun Baijun B Gao Yuan Y Xiao Zhaohui Z Ji Xu X Wang Ruilan R Wu Jianzhong J Wang Xiliang X Zhang Shaogeng S Yang Penghui P

Oncotarget 20171208 90

Hepatocellular carcinoma (HCC) is the most common neoplasm and is a leading cause of cancer-related death. Despite advances in the diagnosis and management of HCC, its prognosis remain unfavorable. Accumulating evidence has shown that long intergenic noncoding RNAs (lincRNAs) play central roles in the development of HCC. In this study, we identified a long intergenic noncoding RNA referred to as lincRNA P7 in HCC and explored its clinical significance and biological functions in HCC. The express ...[more]

PMID: 30546827

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Project description:BackgroundAlthough the prognostic value of lncRNA small nucleolar RNA host gene 15 (SNHG15) expression in cancers has been evaluated in many studies, the results remain controversial. This meta-analysis aimed to clarify the role of SNHG15 in the prognosis of different cancer patients.Materials and methodsEligible studies were selected from PubMed, PMC, EMBASE, Web of Science, and Cochrane Library according to the inclusion and exclusion criteria (up to December 20, 2019). The primary outcome was overall survival (OS) and recurrence-free survival (RFS). The secondary outcome was other clinicopathological parameters (including advanced TNM stage, lymph node metastasis, distant metastases, and gender). The Cancer Genome Atlas (TCGA) dataset was used to verify the analysis results.ResultsEleven eligible studies were eventually included, involving 9 different types of cancer and 1,079 patients. The high expression of SNHG15 was indicative of a significantly poor OS of cancer patients (HR = 1.96, 95% CI = 1.55-2.47, P < 0.00001). Subgroup analysis showed that the high expression of SNHG15 was associated with a significantly poor OS of patients with digestive cancer (HR = 1.91, 95% CI = 1.38-2.66, P=0.0001), but not lung cancer (HR = 1.83, 95% CI = 0.89-3.76, P=0.010). The RFS of patients with high expression of SNHG15 was shorter than that of patients with low expression of SNHG15 (HR = 2.03, 95% CI = 1.46-2.83, P < 0.00001). In addition, high SNHG15 expression level was significantly correlated with later TNM stage (OR = 3.05, 95% CI = 2.31-4.02, P < 0.00001), lymphatic metastasis (OR = 3.20, 95% CI = 2.30-4.45, P < 0.00001), and distant metastasis (OR = 5.05, 95% CI = 2.15-11.85, P=0.0002). The TCGA verification results were consistent with those observed in our meta-analysis.ConclusionHigh expression of the long noncoding RNA SNHG15 in cancer tissue samples predicts an unfavorable prognosis for cancer patients. LncRNA SNHG15 can be used as an adverse prognostic biomarker for cancer patients.

Project description:BackgroundInositol Polyphosphate-5-Phosphatase B (INPP5B), a inositol 5-phosphatase, plays an important role in many biological processes through phosphorylating PI(4,5)P2 and/or PI(3,4,5)P3 at the 5-position. Nevertheless, little is known about its function and cellular pathways in tumors. This study aims to investigate the potential role of INPP5B as a diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD), as well as its biological functions and molecular mechanisms in LUAD.MethodsTCGA, GEO, CTPAC, and HPA datasets were used for differential expression analysis and pathological stratification comparison. The prognostic and diagnostic role of INPP5B was determined by Kaplan-Meier curves, univariate and multivariate Cox regression analysis, and receiver operating characteristics (ROC) curve analyses. The potential mechanism of INPP5B was explored through GO, KEGG, and GSEA enrichment analysis, as well as GeneMANIA and STRING protein-protein interaction (PPI) network. PicTar, PITA, and miRmap databases were used for exploring miRNA targeting INPP5B. In molecular biology experiments, immunohistochemical analyses and Western blot analyses were used to determine protein expression. Co-immunoprecipitation assay was used to detect protein-protein interactions. CCK8 assays and colony formation assays were used for the measurement of cell proliferation. Cell cycle was assessed by PI staining with flow cytometry. Cell migration was performed by Transwell assays and wound healing assays.ResultINPP5B was decreased in LUAD tissues compared with normal adjacent tissues. And the low expression of INPP5B was associated with late-stage pathological features. In addition, INPP5B was found to be a significant independent prognostic and diagnostic factor for LUAD patients. Hsa-miR-582-5p was predicted as a negative regulator of INPP5B mRNA expression. INPP5B was significantly correlated with the expression of PTEN and the activity of PI3K/AKT signaling pathways, as determined by enrichment analysis and PPI network. In vitro experiments partially confirmed the aforementioned findings. INPP5B could interact directly with PTEN. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the AKT pathway.ConclusionOur results demonstrated that INPP5B could inhibit the proliferation and metastasis of LUAD cells. It could serve as a novel diagnostic and prognostic biomarker for LUAD patients. Trial registration LUAD tissues and corresponding para-cancerous tissues were collected from 10 different LUAD patients at Hangzhou First People's Hospital. The Ethics Committee of Hangzhou First People's Hospital has approved this study. (registration number: IIT-20210907-0031-01; registration date: 2021.09.13).

Dataset Information

Decreased long intergenic noncoding RNA P7 predicts unfavorable prognosis and promotes tumor proliferation via the modulation of the STAT1-MAPK pathway in hepatocellular carcinoma.

Publications

Decreased long intergenic noncoding RNA P7 predicts unfavorable prognosis and promotes tumor proliferation via the modulation of the STAT1-MAPK pathway in hepatocellular carcinoma.

Similar Datasets

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