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Long noncoding RNA CASC15 predicts unfavorable prognosis and exerts oncogenic functions in non-small cell lung cancer.

ABSTRACT: BACKGROUND:Aberrant expression of long non-coding RNA cancer susceptibility 15 (lncRNA CASC15) has been documented in various human tumors, and upregulation of CASC15 is closely correlated with cancer progression. However, the expression profile and potential biological functions of lncRNA CASC15 in non-small cell lung cancer (NSCLC) have not been fully characterized. METHODS:The expression levels of CASC15 were assessed by qRT-PCR in human NSCLC tissues and by in situ hybridization in NSCLC tissue microarray. The relationship between CASC15 expression and clinical parameters, as well as prognosis were analyzed and validated in TCGA NSCLC datasets. The biological functions of CASC15 were analyzed by CCK-8 assay, cell migration and invasion assay in NSCLC cell lines in vitro. In addition, a mouse xenograft model was established to evaluate the effect of CASC15 knockdown on NSCLC tumor growth in vivo. Epithelial-mesenchymal transition (EMT) related molecules were examined by western blot and immunohistochemistry staining. RESULTS:We found that CASC15 was upregulated in NSCLC tissues and cell lines. High expression levels of CASC15 were correlated with malignancies and poor survival rate in NSCLC patients. Multivariate analysis revealed that CASC15 was an independent risk factor of prognosis. In addition, we demonstrated that CASC15 knockdown inhibited NSCLC cell proliferation, migration and invasion in vitro. Xenograft model showed CASC15 knockdown significantly suppressed NSCLC tumor growth. Mechanistically, we revealed that CASC15 regulated EMT-related molecules and promoted the NSCLC progression and metastasis. CONCLUSION:In summary, our findings suggest CASC15 exhibits an oncogenic role in promoting NSCLC tumorigenesis via regulating EMT.

SUBMITTER: Li M

PROVIDER: S-EPMC6684884 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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Long noncoding RNA CASC15 predicts unfavorable prognosis and exerts oncogenic functions in non-small cell lung cancer.

Li Min M Chen Yu Y Zhu Jicun J Gao Zhan Z Wang Tao T Zhou Pengli P

American journal of translational research 20190715 7

<h4>Background</h4>Aberrant expression of long non-coding RNA cancer susceptibility 15 (lncRNA CASC15) has been documented in various human tumors, and upregulation of CASC15 is closely correlated with cancer progression. However, the expression profile and potential biological functions of lncRNA CASC15 in non-small cell lung cancer (NSCLC) have not been fully characterized.<h4>Methods</h4>The expression levels of CASC15 were assessed by qRT-PCR in human NSCLC tissues and by <i>in situ</i> hybr ...[more]

PMID: 31396336

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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.

Dataset Information

Long noncoding RNA CASC15 predicts unfavorable prognosis and exerts oncogenic functions in non-small cell lung cancer.

Publications

Long noncoding RNA CASC15 predicts unfavorable prognosis and exerts oncogenic functions in non-small cell lung cancer.

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