title: Up-regulation of long non-coding HOTTIP functions as an oncogene by regulating HOXA13 in non-small cell lung cancer.
abstract: Non-small cell lung cancer (NSCLC) is the major cause of cancer death worldwide. Increasing evidences show that long non coding RNAs (lncRNAs) are widely involved in the development and progression of NSCLC. The lncRNA HOTTIP has been identified as an oncogene in several human cancers, but its role in NSCLC remains unknown. The present study was to determine the expression and function of HOTTIP in NSCLC. Quantitative real-time PCR was used to detect the expressions of HOTTIP in 53 paired NSCLC tissues and cell lines. Furthermore, RNA interference (RNAi) and over-expression approaches were used to investigate the biological function of HOTTIP in lung cancer cell line. The impacts of HOTTIP on cell migration, proliferation and apoptosis were analyzed using wound scratch assay, MTT and flow cytometry, respectively. The results revealed that the HOTTIP expression was significantly up-regulated in NSCLC tissues and cells when compared with corresponding adjacent normal tissues and normal bronchial epithelial cells (p<0.05). Furthermore, knock-down of HOTTIP significantly inhibited cell proliferation, migration and induced cell apoptosis in vitro, while over-expression of HOTTIP led to the opposite effects. In addition, we identified HOTTIP as a transcriptional regulator of HOXA13 in lung cancer cell. Ectopic expression of HOTTIP suppressed the endogenous level of HOXA13, while knock-down of HOTTIP increased HOXA13 expression. Knock-down of HOXA13 by RNA interference (siHOXA13) revealed that HOTTIP promoted lung cell proliferation, migration, and inhibited apoptosis, at least partly by regulating HOXA13. The present study is the first to identify that HOTTIP functions as an oncogene by regulating HOXA13 in NSCLC, which may represent a new biomarker and a potential therapeutic target for NSCLC intervention.
authors.affiliation: Department of Respiratory, The First Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Sang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Fucheng
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Respiratory, The First Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Dongjie
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Respiratory, The First Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Bi
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Xuanxi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hao
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Respiratory, The First Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
keywords: HOTTIP; HOXA13; NSCLC; oncogene