LncRNA Expression Profile Of ?Np63? And Its Molecular Mechanism For Inhibiting LIF Expression In Cervical Cancer

Background:As a member of the p53 family,p63 has twodifferent transcription initiation sites producing proteinswith(TA)or without(DN)an activation domain.According to the different terminus regions,p63 is classified into TAp63?,TAp63?,TA p63?,?Np63?,?Np63?,?Np63?,?Np63?,and ?Np63?[2-4].Not like p53,p63 is not present in various cells and especiallytakes important part inthe processes of epithelium stratification and terminal differentiation.We have reported previously that ??p63? is the predominant isoform expressed in the epithelium of cervix and it decreases innon-keratin differentiation of cervical squamous tumors.LncRNA,a new class of non-coding RNA more than 200 nucleotides in length,has been receiving more attention,especially regarding malignant neoplasm[24].Accumulating evidence has demonstrated that lncRNAs regulate gene expression at a variety of levels,including chromatin modification,transcription,and post-transcription.Deregulation of lncRNAs has also been indicated to contribute to the initiation and progression of some human cancers,including breast cancer,lung adenocarcinomaand cervical cancer.The aims of this study were to determine the mRNA and LncRNA targets of ?Np63? in cervical cancer and molecular programs in cancerous differentiation.Methods:Different expression profiles of the mRNAs and LncRNAs and validation of abnormallyexpressed candidate mRNAs and LncRNAs were assayed in the stable Si Ha cell lines overexpressing p63(Si Ha/?Np63?)and the control cell lines(Si Ha/Con).Results:1.Through mRNA and LncRNA microarrays and qRT-PCR validation,9 LncRNAs regulated by ?Np63? were screened out,including ENST00000447565(Lnc-LIF-AS),TCONS00012062,ENST00000570197,ENST00000563036,TCONS00011964,ENST00000439517,TCONS00004869,TCONS00014003,ENST00000469965.2.After the UCSC analysis of these LncRNAs,we found a target gene,LIF,regulated by Lnc-LIF-AS and ?Np63?.?Np63? can inhibit the LIF expression at the transcriptional level,or by the downregulation of Lnc-LIF-AS.3.Lnc-LIF-AS,an antisense of LIF,overlaps with a 3'-UTR of LIF mRNA and positively regulates the expression of the LIF gene,which might be related to mRNA stability control.Conclusion:1.?Np63? can inhibit the LIF expression by the downregulation of Lnc-LIF-AS.2.?Np63? can suppress the transcription of LIF directly.3.The 3'-UTR of Lnc-LIF-AS may act as a sponge to absord the ncRNAs targeting LIF,thus promoting the LIF expression.