Comprehensive analysis of lncRNAs microarray profile and mRNA-lncRNA co-expression in oncogenic HPV-positive cervical cancer cell lines

• Published in: Oncotarget 2016-08, Vol.7 (31), p.49917-49929
• Main Authors: Yang, LingYun, Yi, Ke, Wang, HongJing, Zhao, YiQi, Xi, MingRong
• Format: Article
• Language: English
• Subjects: Carcinogenesis - genetics; Caspase 3 - metabolism; Cell Line, Tumor; Female; Forkhead Transcription Factors - metabolism; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Rearrangement; Gene Regulatory Networks; HeLa Cells; Human papillomavirus 16; Human papillomavirus 18; Humans; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Research Paper; RNA, Long Noncoding - genetics; RNA, Messenger - metabolism; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - virology
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.10232

Long non-coding RNAs are emerging to be novel regulators in gene expression. In current study, lncRNAs microarray and lncRNA-mRNA co-expression analysis were performed to explore the alternation and function of lncRNAs in cervical cancer cells. We identified that 4750 lncRNAs (15.52%) were differentially expressed in SiHa (HPV-16 positive) (2127 up-regulated and 2623 down-regulated) compared with C-33A (HPV negative), while 5026 lncRNAs (16.43%) were differentially expressed in HeLa (HPV-18 positive) (2218 up-regulated and 2808 down-regulated) respectively. There were 5008 mRNAs differentially expressed in SiHa and 4993 in HeLa, which were all cataloged by GO terms and KEGG pathway. With the help of mRNA-lncRNA co-expression network, we found that ENST00000503812 was significantly negative correlated with RAD51B and IL-28A expression in SiHa, while ENST00000420168, ENST00000564977 and TCONS_00010232 had significant correlation with FOXQ1 and CASP3 expression in HeLa. Up-regulation of ENST00000503812 may inhibit RAD51B and IL-28A expression and result in deficiency of DNA repair pathway and immune responses in HPV-16 positive cervical cancer cell. Up-regulation of ENST00000420168, ENST00000564977 and down-regulation of TCONS_00010232 might stimulate FOXQ1 expression and suppress CASP3 expression in HPV-18 positive cervical cancer cell, which lead to HPV-induced proliferation and deficiency in apoptosis. These results indicate that changes of lncRNAs and related mRNAs might impact on several cellular pathways and involve in HPV-induced proliferation, which enriches our understanding of lncRNAs and coding transcripts anticipated in HPV oncogenesis of cervical cancer.