LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa‐mir‐22‐3p

Journal of Cellular Physiology - Tập 233 Số 5 - Trang 4126-4136 - 2018
Huixing Dong1, Ren Wang1, Xiaoyan Jin1, Jian Zeng1, Jing Pan1
1Department of Respiratory Medicine Tongren Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China

Tóm tắt

Long non‐coding RNAs (lncRNAs) serve critical roles in the pathogenesis of various cancers, including lung adenocarcinoma (LUAD). Herein, in this study, we aimed to investigate the biological and clinical significance of lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) in LUAD. It was observed that DGCR5 was upregulated in LUAD tissues and LUAD cell lines. Inhibition of DGCR5 can prevent LUAD progression via playing anti‐apoptosis roles. Both mRNA expression and protein levels of BCL‐2 were increased by DGCR5 downregulation while reversely BAX was increased. Additionally, a novel microRNA target of DGCR5, hsa‐mir‐22‐3p was identified through bioinformatics search and confirmed by dual‐luciferase reporter system. Gain and loss‐of‐function studies were performed to verify whether DGCR5 exerts its biological functions through regulating hsa‐mir‐22‐3p in vitro. Overexpression of DGCR5 was able to reverse the tumor inhibitory effect of hsa‐mir‐22‐3p mimics. Furthermore, in vivo tests tumor xenografts were established to detect the function of DGCR5 in LUAD tumorigenesis. Downregulated DGCR5 expression was greatly associated with smaller tumor size, implying a favorable prognosis of LUAD patients. Taken these together, DGCR5 could be considered as a prognostic biomarker and therapeutic target in LUAD diagnosis and treatment.

Từ khóa


Tài liệu tham khảo

Ballantyne R. L., 2016, Genome‐wide interrogation reveals hundreds of long intergenic noncoding RNAs that associate with cardiometabolic traits, Human Molecular Genetics, 25, 3125

10.3390/ijms17030356

10.1155/2017/7243968

10.18632/oncotarget.18204

10.1186/s12935-017-0433-7

Cui J., 2015, C‐Myc‐activated long non‐coding RNA H19 downregulates miR‐107 and promotes cell cycle progression of non‐small cell lung cancer, International Journal of Clinical and Experimental Pathology, 8, 12400

10.1126/science.1191138

10.5306/wjco.v5.i2.134

10.1007/s13277-015-3346-x

10.3892/ol.2017.5674

10.1038/cddis.2015.30

Huan J., 2017, Long noncoding RNA CRNDE activates Wnt/beta‐catenin signaling pathway through acting as a molecular sponge of microRNA‐136 in human breast cancer, American Journal of Translational Research, 9, 1977

10.1159/000452582

10.15252/emmm.201707779

10.21037/cco.2017.03.01

10.1186/s12943-017-0674-z

10.2119/molmed.2011.00008

10.1186/s13058-017-0853-2

10.18632/oncotarget.9712

10.1016/j.nbd.2011.12.006

10.3892/ol.2017.6006

Li D. S., 2016, Identification of key long non‐coding RNAs as competing endogenous RNAs for miRNA‐mRNA in lung adenocarcinoma, European Review for Medical and Pharmacological Sciences, 20, 2285

10.3892/or.2017.5579

10.1038/srep20121

10.1186/1471-2407-13-464

Liu Z. H., 2014, Interleukin 7 signaling prevents apoptosis by regulating bcl‐2 and bax via the p53 pathway in human non‐small cell lung cancer cells, International Journal of Clinical and Experimental Pathology, 7, 870

10.1016/j.bbagrm.2015.06.015

10.1177/1010428317701632

10.1159/000438577

10.1186/s12935-016-0380-8

10.18632/oncotarget.18422

10.1177/1758834017704329

10.1016/j.bbrc.2013.05.101

10.3892/ol.2017.6021

10.1007/s11060-014-1613-0

10.3322/caac.21166

10.18632/oncotarget.2934

10.1016/j.febslet.2015.08.046

10.1038/nature12986

10.1038/nrd4018

10.1101/gad.1800909

10.1186/s12943-017-0675-y

10.12659/MSM.901381

10.18632/oncotarget.18059

10.1002/jcb.26145

Yong S., 2017, Reciprocal regulation of DGCR5 and miR‐320a affects the cellular malignant phenotype and 5‐FU response in pancreatic ductal adenocarcinoma, Oncotarget

10.1016/j.semcdb.2014.05.015

10.4103/0019-509X.154055

10.3892/etm.2017.4433

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Thông tin xuất bản

Journal of Cellular Physiology

Tập 233 Số 5

4126-4136

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