Increased expression of LINC01510 predicts poor prognosis and promotes malignant progression in human non-small cell lung cancer

Biomed Pharmacother. 2019 Jan:109:519-529. doi: 10.1016/j.biopha.2018.10.136. Epub 2018 Nov 3.

Abstract

Non-small cell lung cancer (NSCLC), the most prevalent type of lung cancer, is one of the most leading causes of cancer-related morbidity and mortality worldwide. Evidence is accumulating that long non-coding RNAs (lncRNAs) play vital regulatory roles in tumor development and progression. LINC01510, a novel tumor-related lncRNA, has been identified as an oncogene in colorectal cancer; however, its role in NSCLC remains poorly understood. This study aimed to characterize the biological role of LINC01510 in NSCLC and illuminate the molecular mechanisms. Here we found that LINC01510 was highly expressed in NSCLC tissues. Besides, Fisher's exact test showed that high expression of LINC01510 was associated with larger tumor size, advanced TNM stage and lymph node metastasis. Kaplan-Meier survival analysis showed that patients with high LINC01510 expression had a much lower overall survival rate. Gain- and loss-of-function approaches were employed to investigate the effects of LINC01510 on NSCLC cell phenotypes. Functional studies demonstrated that LINC01510 over-expression promoted NSCLC cell proliferation, cell cycle progression, migration and invasion, but shRNA-mediated LINC01510 depletion inhibited NSCLC cell proliferation, cell cycle progression, migration and invasion. Notably, LINC01510 ablation suppressed tumorigenicity of NSCLC cells in a murine xenograft model. Furthermore, mechanistic studies revealed that LINC01510 exerted its oncogenic functions in NSCLC through miR-339-5p-mediated regulation of CDK14. To sum up, our data indicate that increased expression of LINC01510 predicts poor prognosis and promotes tumorigenesis in NSCLC. Collectively, this study may provide a basis for LINC01510 as a candidate therapeutic target in NSCLC.

Keywords: LINC01510; Malignant progression; Non-small cell lung cancer; Poor prognosis.

MeSH terms

  • A549 Cells
  • Aged
  • Animals
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Prognosis
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics

Substances

  • RNA, Long Noncoding