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Upregulated expression of long non-coding RNA LINC00982 regulates cell proliferation and its clinical relevance in patients with gastric cancer

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Tumor Biology

Abstract

Emerging evidences indicate that dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker or potential therapeutic targets. Therefore, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. In this study, we identified a novel lncRNA LINC00982, whose expression was downregulated in tumor tissues in 106 patients with gastric cancer (GC) compared with those in the adjacent normal tissues (P < 0.001). Furthermore, decreased LINC00982 expression was negatively correlated with invasion depth (P < 0.001), advanced TNM stage (P = 0.004), and regional lymph node metastasis (P = 0.005). LINC00982 levels were robust in differentiating gastric cancer tissues from controls [area under the curve (AUC) = 0.742; 95 % confidence interval (CI) = 0.678–0.800, P < 0.01]. Kaplan–Meier analysis demonstrated that decreased LINC00982 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that LINC00982 could be an independent prognostic marker. The levels of LINC00982 in gastric juice from gastric patients were significantly lower than those from normal subjects (P = 0.026). Furthermore, knockdown of LINC00982 expression by small interfering RNA (siRNA) could promote cell proliferation and cell cycle progression, while ectopic expression of LINC00982 inhibited cell proliferation and rendered cell cycle arrest in GC cells partly via regulating P15 and P16 protein expressions. Our findings present that decreased lncRNA LINC00982 could be identified as a poor prognostic biomarker in GC and regulate cell proliferation.

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Conflicts of interest

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Ethics approval and consent to participate

The study was approved by the Ethics Committee on Human Research of the First Affiliated Hospital of Wenzhou Medical University, Huai’an First People’s Hospital, and Yangzhou No.1 People’s Hospital, and written informed consent was obtained from all patients.

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Correspondence to Cong-ying Xie.

Additional information

Zheng-hua Fei, Xiao-juan Yu, and Ming Zhou should be regarded as joint first authors.

Zheng-hua Fei, Xiao-juan Yu and Ming Zhou contributed equally to this work.

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Table S1

Primers used for qRT-PCR. (XLS 16 kb)

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Fei, Zh., Yu, Xj., Zhou, M. et al. Upregulated expression of long non-coding RNA LINC00982 regulates cell proliferation and its clinical relevance in patients with gastric cancer. Tumor Biol. 37, 1983–1993 (2016). https://doi.org/10.1007/s13277-015-3979-9

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  • DOI: https://doi.org/10.1007/s13277-015-3979-9

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