Knockdown of circPRKCA Restrained Cell Growth, Migration, and Invasion of NSCLC Cells Both in vitro and in vivo via Regulating miR-330-5p/PDK1/AKT Pathway

被引:10
作者
Bai, Lanxiang [1 ]
Peng, Xiaonu [2 ]
Sun, Ruimei [3 ]
机构
[1] Yantai Yuhuangding Hosp, Disinfect Supply Ctr, Yantai 264000, Shandong, Peoples R China
[2] Yantai Yuhuangding Hosp, Dept Thorac Surg, Yantai 264000, Shandong, Peoples R China
[3] Weifang 2 Peoples Hosp, Dept Lab, Weifang 261041, Shandong, Peoples R China
关键词
circPRKCA; miR-330-5p; PDK1; AKT; NSCLC; LUNG-CANCER; PROLIFERATION; PROGRESSION; SUPPRESSES; EXPRESSION;
D O I
10.2147/CMAR.S258370
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Protein kinase Ca (PRKCA) is an oncogene in multiple cancers including non-small-cell lung cancer (NSCLC) and can be transcribed into a number of circular PRKCAs (circPRKCAs). Here, we aimed to elaborate the role and mechanism of circPRKCA_024 (circPRKCA) in malignant progression of NSCLC. Methods: Expression of circPRKCA, miRNA (miR)-330-5p and 3-phosphoinositide-dependent protein kinase-1 (PDK1) was measured by real-time quantitative PCR and Western blotting, and their relationship was testified by dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay. Cell behaviors were evaluated by cell counting kit (CCK)-8, flow cytometry, and transwell assays. AKT activity was confirmed by Western blotting. Xenograft experiment assessed tumor growth. Results: Expression of circPRKCA and PDK1 was upregulated, and miR-330-5p was downregulated in NSCLC tissues and cell lines. High circPRKCA was correlated with TNM stage and lymph node metastasis of NSCLC patients. Silencing circPRKCA could suppress cell viability, migration, and invasion in A549 and H1299 cells, accompanied with apoptosis rate promotion. Moreover, circPRKCA knockdown retarded tumor growth of A549 cells in vivo. Molecularly, miR-330-5p was sponged by circPRKCA, and PDK1 was a target of miR-330-5p. Inhibiting miR-330-5p could attenuate the suppression of circPRKCA knockdown on cell growth, migration, and invasion; contrarily, promoting miR-330-5p caused inhibition on those cell behaviors by downregulating PDK1. Analogously, AKT activity was suppressed by circPRKCA downregulation and miR-330-5p upregulation in NSCLC cells both in vitro and in vivo. Conclusion: Depleting circPRKCA inhibited PDK1 to suppress NSCLC cell malignant behaviors through miR-330-5p/PDK1/AKT pathway.
引用
收藏
页码:9125 / 9137
页数:13
相关论文
共 45 条
[1]   Prevention and Early Detection for NSCLC: Advances in Thoracic Oncology 2018 [J].
Balata, Haval ;
Fong, Kwun M. ;
Hendriks, Lizza E. ;
Lam, Stephen ;
Ostroff, Jamie S. ;
Peled, Nir ;
Wu, Ning ;
Aggarwal, Charu .
JOURNAL OF THORACIC ONCOLOGY, 2019, 14 (09) :1513-1527
[2]   MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma [J].
Bibby, Becky A. S. ;
Reynolds, John V. ;
Maher, Stephen G. .
PLOS ONE, 2015, 10 (07)
[3]   Comprehensive analysis of circular RNAs in pathological states: biogenesis, cellular regulation, and therapeutic relevance [J].
Braicu, Cornelia ;
Zimta, Andreea-Alina ;
Gulei, Diana ;
Olariu, Andrei ;
Berindan-Neagoe, Ioana .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2019, 76 (08) :1559-1577
[4]  
Cognini R, 2013, IN C IND ENG ENG MAN, P1, DOI 10.1109/IEEM.2013.6962363
[5]   lncRNA PCACAT6 promotes non-small cell lung cancer cell proliferation, migration and invasion through regulating miR-330-5p [J].
Cui, Li Hua ;
Xu, Hai Rong ;
Yang, Wu ;
Yu, Li Jiang .
ONCOTARGETS AND THERAPY, 2018, 11 :7715-7724
[6]   Circular RNAs and RNA Splice Variants as Biomarkers for Prognosis and Therapeutic Response in the Liquid Biopsies of Lung Cancer Patients [J].
de Fraipont, Florence ;
Gazzeri, Sylvie ;
Cho, William C. ;
Eymin, Beatrice .
FRONTIERS IN GENETICS, 2019, 10
[7]   Serine/Threonine Kinase 3-Phosphoinositide-Dependent Protein Kinase-1 (PDK1) as a Key Regulator of Cell Migration and Cancer Dissemination [J].
Di Blasio, Laura ;
Gagliardi, Paolo A. ;
Puliafito, Alberto ;
Primo, Luca .
CANCERS, 2017, 9 (03)
[8]   MiR-199a suppresses the hypoxia-induced proliferation of non-small cell lung cancer cells through targeting HIF1α [J].
Ding, Gang ;
Huang, Gang ;
Liu, He-dai ;
Liang, Hong-xiang ;
Ni, Yu-feng ;
Ding, Zhao-heng ;
Ni, Guo-ying ;
Hua, Hong-wei .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2013, 384 (1-2) :173-180
[9]   RETRACTED: miR-330-5p suppresses glioblastoma cell proliferation and invasiveness through targeting ITGA5 (Retracted Article) [J].
Feng, Linsen ;
Ma, Jianhua ;
Ji, Haiming ;
Liu, Yichun ;
Hu, Weixing .
BIOSCIENCE REPORTS, 2017, 37
[10]   A novel plasma circular RNA circFARSA is a potential biomarker for non-small cell lung cancer [J].
Hang, Dong ;
Zhou, Jing ;
Qin, Na ;
Zhou, Wen ;
Ma, Hongxia ;
Jin, Guangfu ;
Hu, Zhibin ;
Dai, Juncheng ;
Shen, Hongbing .
CANCER MEDICINE, 2018, 7 (06) :2783-2791