Dissertation > Medicine, health > Oncology > Respiratory system tumors > Lung tumors

Inhibition Functions and Mechanisms of Decreased miR-155Expression on Lung Adenocarcinoma

Author JiangWenYang
Tutor FuXiangNing
School Huazhong University of Science and Technology
Course Surgery
Keywords miR-155 TP53INP1 Lung adeno carcinoma Cisplatin Proliferation Apoptosis
CLC R734.2
Type PhD thesis
Year 2013
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Objective:Lung cancer is one of the malignant tumors with the highest morbidity and mortality rate in the globe. Comprehensive treatment based on surgery couldlargely improve the prognosis of lung cancer, the overall effect, however, is still poor. New and effective treatment options for lung cancer are urgently needed. miRNA is a non-protein coding small RNA, it could exert its functions by regulating the expression of target genes and become a hot field of life science research in recent years.miR-155is such a typical and multifunctional miRNA, it could promote the development and progression of a variety of malignant tumors, but the expressions and mechanisms of miR-155on lung cancer remain controversial.In this study, we tend to investigate the impacts and possible mechanisms of miR-155on the biological characteristics of lung adenocarcinoma, and observe the synergistic functions of combination of miR-155inhibitor and cisplatin on the treatment of lung adenocarcinoma, and provide new suggestions for the treatment of lung adenocarcinoma.Methods:We evaluated the expression of miR-155and its target TP53INP1in25paired lung adenocarcinoma tissues and adjacent normal lung tissues by quantitative real-time polymerase chain reaction, imrriunohistochemistry and Western Blot, and then examined the correlation between miR-155and TP53INP1. In order to investigate the impacts of miR-155on the biological characteristics of lung adenocarcinoma, we transfected lung adenocarcinoma cells with miR-155inhibitor, then the proliferation and apoptosis related critical proteins were tested by Western Blot and the impacts of miR-155inhibitor alone or combined with cisplatin on proliferation and apoptosis of lung adenocarcinoma cells were tested by CCK-8and flow cytometry.Results:Increased expression of miR-155was associated with decreased expression of TP53INPlin lung adenocarcinoma tissues. miR-155inhibitor could suppress proliferation and induce apoptosis in lung adenocarcinoma cells, the possible mechanismswere both PI3K/AKT and MAPK/ERK pathways were inhibited and expression of Bcl-2protein was decreased and expression of Bax protein was increased.The combination of miR-155inhibitor and cisplatin has a synergistic effect on the treatment of lung adenocarcinoma.Conclusions:miR-155changes the biological characteristics of lung adenocarcinoma by negatively regulatingthe expression of TP53INP1. miR-155inhibitor alone or combined with cisplatin is a potential treatment method for lung adenocarcinoma.

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