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HOTTIP 的过表达通过调节 AKT 信号通路促进肺腺癌的增殖和耐药性。

Overexpression of HOTTIP promotes proliferation and drug resistance of lung adenocarcinoma by regulating AKT signaling pathway.

机构信息

Department of Thoracic Surgery, Jining No. 1 People's Hospital, Jining, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Dec;21(24):5683-5690. doi: 10.26355/eurrev_201712_14013.

DOI:10.26355/eurrev_201712_14013
PMID:29272003
Abstract

OBJECTIVE

Lung adenocarcinoma is an important pathological type of lung cancer. Drug resistance is the main reason for failure of lung adenocarcinoma therapy. The purpose of this study is to explore the role of HOTTIP in the progression of lung adenocarcinoma and in drug resistance.

PATIENTS AND METHODS

Differentially expressed lncRNAs in normal lung tissues and lung adenocarcinoma tissues were analyzed in The Cancer Genome Atlas (TCGA) database, followed by analysis of differential lncRNAs in treated sensitive and insensitive groups. HOTTIP was found to be highly expressed in lung adenocarcinoma tissues and in drug-resistant tissues. Next, the expression of HOTTIP in clinical samples and its relation to clinical data were analyzed. Then, we examined the effect of HOTTIP in lung adenocarcinoma by detecting changes in cell proliferation and drug resistance after overexpression and interference with HOTTIP.

RESULTS

By analyzing the normal and lung adenocarcinoma tissues from TCGA database and the treatment of sensitive and insensitive samples, we found that HOTTIP was overexpressed in lung adenocarcinoma and significantly increased in the treatment-insensitive group. Similar results were obtained in clinical samples. In order to explore the role of HOTTIP in lung adenocarcinoma, the proliferation ability of A549 and the drug resistance of A549/PA were significantly reduced after interfering with HOTTIP. Overexpression of HOTTIP, proliferation ability of A549 and drug resistance of A549/PA was significantly enhanced.

CONCLUSIONS

HOTTIP can promote the progression of lung adenocarcinoma, and the formation of lung adenocarcinoma resistance regulated by the protein kinase B (AKT) signaling pathway.

摘要

目的

肺腺癌是肺癌的重要病理类型。耐药是肺腺癌治疗失败的主要原因。本研究旨在探讨 HOTTIP 在肺腺癌进展和耐药中的作用。

患者和方法

分析 TCGA 数据库中正常肺组织和肺腺癌组织中差异表达的 lncRNA,然后分析处理敏感和不敏感组中差异 lncRNA。发现 HOTTIP 在肺腺癌组织和耐药组织中高表达。接下来,分析临床样本中 HOTTIP 的表达及其与临床资料的关系。然后,通过检测过表达和干扰 HOTTIP 后细胞增殖和耐药性的变化,研究 HOTTIP 对肺腺癌的影响。

结果

通过分析 TCGA 数据库中的正常和肺腺癌组织以及敏感和不敏感样本的处理情况,我们发现 HOTTIP 在肺腺癌中过度表达,并且在治疗不敏感组中显著增加。在临床样本中也得到了类似的结果。为了探讨 HOTTIP 在肺腺癌中的作用,干扰 HOTTIP 后 A549 的增殖能力和 A549/PA 的耐药性明显降低。而过表达 HOTTIP 后,A549 的增殖能力和 A549/PA 的耐药性明显增强。

结论

HOTTIP 可促进肺腺癌的进展,并通过蛋白激酶 B(AKT)信号通路调节肺腺癌耐药的形成。

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