The long noncoding RNA HOTAIR has tissue and cell type-dependent effects on HOX gene expression and phenotype of urothelial cancer cells

ABSTRACTLong noncoding RNAs have emerged as abundant and important regulators of gene expression in diverse animals. In D. melanogaster several lncRNAs involved in regulating Hox gene expression in the Bithorax Complex have been reported. However, no functional Hox long noncoding RNAs have been described in the Antennapedia Complex. Here we have characterized a long noncoding RNA lincX from the Antennapedia Complex, that is transcribed from previously identified cis-regulatory sequences of the Hox gene Sex combs reduced (Scr). We use both the GAL4-UAS system and mutants to ectopically overexpress the lincX RNA from exogenous and endogenous loci respectively, in order to dissect the potential regulatory functions of lincX RNA versus lincX transcription. Our findings suggest that transcription through the lincX locus, but not the lincX RNA itself, may facilitate initiation of Scr in cis in the early embryo. Transvection phenomena, where regulatory sequences on one chromosome can affect expression on the homolog, have previously been reported in genetic studies of Scr. By analysing lincX and Scr nascent transcriptional sites in embryos heterozygous for a gain of function mutation, we directly visualize this transvection, and observe that the ectopic lincX transcriptional state appears to be relayed in trans to the homologous wild-type chromosome. This trans-activation of lincX correlates with both ectopic activation of Scr in cis, and increased chromosomal proximity. Our results are consistent with a model whereby early long noncoding RNA transcription through cis-regulatory sequences can be communicated between chromosomes, and facilitates long-range initiation of Hox gene expression in cis.

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Long Noncoding RNA HOTAIRM1 Maintains Tumorigenicity of Glioblastoma Stem-Like Cells Through Regulation of HOX Gene Expression

Neurotherapeutics ◽

10.1007/s13311-019-00799-0 ◽

2019 ◽

Vol 17 (2) ◽

pp. 754-764 ◽

Cited By ~ 2

Author(s):

Hongping Xia ◽

Yinhua Liu ◽

Zhichun Wang ◽

Wei Zhang ◽

Min Qi ◽

...

Keyword(s):

Gene Expression ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Hox Gene

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Human Papillomavirus E6/E7 and Long Noncoding RNA TMPOP2 Mutually Upregulated Gene Expression in Cervical Cancer Cells

Journal of Virology ◽

10.1128/jvi.01808-18 ◽

2019 ◽

Vol 93 (8) ◽

Cited By ~ 15

Author(s):

Hongpeng He ◽

Xiang Liu ◽

Yue Liu ◽

Mengmeng Zhang ◽

Yongwei Lai ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Cervical Cancer ◽

Human Papillomavirus ◽

Cancer Cells ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Human Papillomaviruses ◽

Cervical Cancer Cells ◽

E6 And E7

ABSTRACT TMPOP2 was previously suggested to be an oncogenic long noncoding RNA which is excessively expressed in cervical cancer cells and inhibits E-cadherin gene expression by recruiting transcription repressor EZH2 to the gene promoter. So far, the function and regulation of TMPOP2 in cervical cancer remain largely unknown. Herein, we found that TMPOP2 expression was correlated with human papillomavirus 16/18 (HPV16/18) E6 and E7 in cervical cancer cell lines CaSki and HeLa. Tumor suppressor p53, which is targeted for degradation by HPV16/18, was demonstrated to associate with two p53 response elements in the TMPOP2 promoter to repress the transcription of the TMPOP2 gene. Reciprocally, ectopic expression of TMPOP2 was demonstrated to sequester tumor repressor microRNAs (miRNAs) miR-375 and miR-139 which target HPV16/18 E6/E7 mRNA and resulted in an upregulation of HPV16/18 E6/E7 genes. Thereby, HPV16/18 E6/E7 and the long noncoding RNA (lncRNA) TMPOP2 form a positive feedback loop to mutually derepress gene expression in cervical cancer cells. Moreover, results of RNA sequencing and cell cycle analysis showed that knockdown of TMPOP2 impaired the expression of cell cycle genes, induced cell cycle arrest, and inhibited HeLa cell proliferation. Together, our results indicate that TMPOP2 and HPV16/18 E6/E7 mutually strengthen their expression in cervical cancer cells to enhance tumorigenic activities. IMPORTANCE Human papillomaviruses 16 and 18 (HPV16/18) are the main causative agents of cervical cancer. Viral proteins HPV16/18 E6 and E7 are constitutively expressed in cancer cells to maintain oncogenic phenotypes. Accumulating evidences suggest that HPVs are correlated with the deregulation of long noncoding RNAs (lncRNAs) in cervical cancer, although the mechanism was unexplored in most cases. TMPOP2 is a newly identified lncRNA excessively expressed in cervical cancer. However, the mechanism for the upregulation of TMPOP2 in cervical cancer cells remains largely unknown and its relationship with HPVs is still elusive. The significance of our research is in revealing the mutual upregulation of HPV16/18 E6/E7 and TMPOP2 with the molecular mechanisms explored. This study will expand our understandings of the oncogenic activities of human papillomaviruses and lncRNAs.

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