The long non-coding RNA HOTTIP promotes the proliferation of non-small cell lung cancer cells through the regulation of apoptosis

周发忱; 赵　磊; 白宇新

doi:10.3969/j.issn.1007-3969.2015.09.002

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The long non-coding RNA HOTTIP promotes the proliferation of non-small cell lung cancer cells through the regulation of apoptosis

更新时间：2025-12-31

- The long non-coding RNA HOTTIP promotes the proliferation of non-small cell lung cancer cells through the regulation of apoptosis
- China Oncology Vol. 25, Issue 9, Pages: 652-658(2015)
- 作者机构：
  
  1. 大连医科大学附属第一医院胸外科,辽宁,大连,116011
  2. 大连医科大学组织胚胎学教研室,辽宁,大连,116044
- 作者简介：
- 基金信息：
- DOI：10.3969/j.issn.1007-3969.2015.09.002
  CLC：
- Published Online：15 December 2015，
  
  Published：15 December 2015
- 稿件说明：
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周发忱,赵　磊,白宇新,等. 长链非编码RNA HOTTIP 通过调控细胞凋亡水平促进非小细胞肺癌增殖[J]. 中国癌症杂志, 2015, 25(9): 652-658.

周发忱, 赵　磊, 白宇新. The long non-coding RNA HOTTIP promotes the proliferation of non-small cell lung cancer cells through the regulation of apoptosis[J]. China Oncology, 2015, 25(9): 652-658.
周发忱,赵　磊,白宇新,等. 长链非编码RNA HOTTIP 通过调控细胞凋亡水平促进非小细胞肺癌增殖[J]. 中国癌症杂志, 2015, 25(9): 652-658. DOI： 10.3969/j.issn.1007-3969.2015.09.002.

周发忱, 赵　磊, 白宇新. The long non-coding RNA HOTTIP promotes the proliferation of non-small cell lung cancer cells through the regulation of apoptosis[J]. China Oncology, 2015, 25(9): 652-658. DOI： 10.3969/j.issn.1007-3969.2015.09.002.

摘要

背景与目的：探索非小细胞肺癌(non-small cell lung cancer，NSCLC)有效的早期诊断及预后标志物具有重要的科学意义和临床价值。长链非编码RNA(lncRNA)在肿瘤中的作用逐渐引起研究者的关注。本研究拟分析lncRNA HOTTIP在NSCLC中的表达情况及对NSCLC细胞增殖水平的影响和机制。方法：采用实时定量PCR(quantitative real-time PCR，qRT-PCR)检测方法检测54例NSCLC组织及其对应癌旁组织的HOTTIP表达情况，分析NSCLC组织HOTTIP表达与临床病理参数的相关性；MTT方法检测肺癌细胞增殖水平，流式细胞术检测凋亡率的改变；蛋白［质］印迹法(Western blot)检测目的基因的蛋白表达变化。结果：与癌旁组织比较，HOTTIP在肺癌组织中的表达率明显增加，差异有统计学意义(P0.05)。HOTTIP表达与患者淋巴结转移和TNM分期相关。转染HOTTIP siRNA至A549肺癌细胞后，结果显示，与未转染组和阴性质粒转染组相比，转染siRNA-HOTTIP 的A549细胞HOTTIP 表达明显降低；HOTTIP表达下调后细胞增殖速度减慢，凋亡率增加，凋亡相关蛋白Bax的表达增加，Bcl-2表达减少。结论：HOTTIP是一种新的NSCLC生物标志物，可作为潜在的治疗新靶点。

Abstract

Background and purpose: Exploration of the effective early diagnostic and prognostic markers of non-small cell lung cancer (NSCLC) has important scientific significance and clinical value. Recently

the role of long chain non-coding RNA (lncRNA) in the tumor attracts widespread attention. This study intended to investigate the level of lncRNA HOTTIP in NSCLC

the effect of HOTTIP on cell proliferation and its mechanisms. Methods: Expression of lncRNA HOTTIP in tumor and their matched non-tumor tissues were determined by quantitative real-time PCR (qRT-PCR) in NSCLC patients. Then

we analyzed the potential correlation of lncRNA HOTTIP expression levels in tumor tissues with clinicopathological features of NSCLC and clinical outcome. The effects of HOTTIP on NSCLC cell proliferation and apoptosis were tested using in vitro MTT and flow cytometric assays. Western blot method was uesd to detect the expressions of proteins. Results: LncRNA HOTTIP expression level was significantly decreased in NSCLC tissues in comparison to adjacent non-tumor tissues (P0.05). It was also proved that HOTTIP expression was associated with NSCLC histological grade and lymph node metastasis. Moreover

knockdown of HOTTIP expression in A549 cell line decreased proliferation and enhanced apoptosis compared with transfected negative control. Western blot assay showed that the level of Bax protein was significantly increased

whereas Bcl-2 was significantly decreased in HOTTIP- silencing A549 cell. Conclusion: HOTTIP is a novel prognostic biomarker and a potential therapeutic candidate for NSCLC.

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