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LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma.

ABSTRACT: OBJECTIVE:Accumulating data show that dysregulation of long noncoding RNAs (lncRNAs) acts a critical role in a variety of malignancies. Among these lncRNAs, small nucleolar RNA host genes (SNHGs) are associated with tumour growth and progression. But, the molecular mechanisms by which SNHG4 contributes to osteosarcoma remain undocumented. METHODS:The association between lncRNA SNHG4 expression and clinicopathologic characteristics and prognosis in patients with osteosarcoma was analysed by TCGA RNA-sequencing data. Cell viability and colony formation abilities were respectively assessed by MTT and colony formation assays. LncRNA SNHG4-specific binding with miR-224-3p was verified by bioinformatic analysis, luciferase gene report, and RNA immunoprecipitation assays. Regulation relationship between SNHG4 and miR-224-3p expression was further evaluated by the rescue experiments. RESULTS:The expression level of lncRNA SNHG4 was significantly elevated in osteosarcoma samples and cell lines as compared with the adjacent normal tissues, and SNHG4 high expression was associated with tumour size (TS) and poor prognosis in patients with osteosarcoma. Knockdown of SNHG4 suppressed cell viability and invasive potential, whereas ectopic SNHG4 expression displayed the opposite effects. Moreover, we found that lncRNA SNHG4 acted as a sponge of miR-224-3p, and miR-224-3p mimic reversed SNHG4 induced tumour-promoting effects in osteosarcoma cells. The expression of miR-224-3p depicted a negative correlation with SNHG4 in osteosarcoma samples and miR-224-3p low expression was associated with TS and poor survival in patients with osteosarcoma. CONCLUSION:Our findings demonstrated that LncRNA SNHG4 promoted tumour growth by sponging miR-224-3p and represented a poor prognostic factor in patients with osteosarcoma.

SUBMITTER: Xu R

PROVIDER: S-EPMC6528889 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma.

Xu Ruida R Feng Fan F Yu Xiaosheng X Liu Zude Z Lao Lifeng L

Cell proliferation 20180828 6

<h4>Objective</h4>Accumulating data show that dysregulation of long noncoding RNAs (lncRNAs) acts a critical role in a variety of malignancies. Among these lncRNAs, small nucleolar RNA host genes (SNHGs) are associated with tumour growth and progression. But, the molecular mechanisms by which SNHG4 contributes to osteosarcoma remain undocumented.<h4>Methods</h4>The association between lncRNA SNHG4 expression and clinicopathologic characteristics and prognosis in patients with osteosarcoma was an ...[more]

PMID: 30152090

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Project description:Background & aimsIntrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide with an increasing incidence and limited therapeutic options. Therefore, there is an urgent need to open the field to new concepts for identifying clinically relevant therapeutic targets and biomarkers. Here, we explored the role and the clinical relevance of circular RNA (circRNA) circLTBP2 in iCCA.MethodsTransforming growth factor β (TGFβ)-regulated circRNAs were identified by dedicated microarrays in human HuCC-T1 iCCA cell line, and their clinical relevance was evaluated in independent cohorts of patients. Gain and loss of function of circLTBP2 combined with functional tests was performed in vitro and in vivo in mice. RNA pulldown, microRNA sequencing, and RNA immunoprecipitation were performed to explore the sponging activity of circLTBP2.ResultsCircLTBP2 (has_circ_0032603) was identified as a novel TGFβ-induced circRNA in several cholangiocarcinoma cell lines. CircLTBP2 promotes tumour cell proliferation, migration, and resistance to gemcitabine-induced apoptosis in vitro and tumour growth in vivo. Mechanistically, circLTBP2 acts as a competitive RNA regulating notably the activity of the tumour suppressor microRNA miR-338-3p, leading to the overexpression of its pro-metastatic targets. The restoration of miR-338-3p levels in iCCA cells reversed the pro-tumourigenic effects driven by circLTBP2, including the resistance to gemcitabine-induced apoptosis. In addition, circLTBP2 expression predicted a reduced survival, as detected in not only tumour tissues but also serum extracellular vesicles isolated from patients with iCCA.ConclusionsCircLTBP2 is a novel effector of the pro-tumourigenic arm of TGFβ and a clinically relevant biomarker easily detected from liquid biopsies in iCCA.Impact and implicationsIntrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer with limited therapeutic options. Opening the field to new concepts is urgently needed to improve the survival of patients. Here, we evaluated the role and the clinical relevance of circular RNA. We report that TGFβ-induced circLTBP2 contributes to CCA carcinogenesis and may constitute a clinically relevant prognostic biomarker detected in liquid biopsies.

Dataset Information

LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma.

Publications

LncRNA SNHG4 promotes tumour growth by sponging miR-224-3p and predicts poor survival and recurrence in human osteosarcoma.

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