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Natural antisense transcripts (NAT) are prevalent phenomena in the mammalian genome and play significant regulatory roles in gene expression. While new insights into NAT continue to be revealed, their exact function and their underlying mechanisms in human cancer remain largely unclear. We identified a NAT of CDK4, referred to TSPAN31, which inhibits CDK4 mRNA and protein expression in human cervical cancer by targeting the 3'-untranslated region (3'-UTR) of the CDK4 mRNA. Furthermore, silencing the expression of the TSPAN31 mRNA rescued the TSPAN31 3'-UTR- or the TSPAN31 full-length-induced decrease in CDK4 expression. Noteworthy, we discovered that TSPAN31, as a member of the tetraspanin family, suppressed cell proliferation by down-regulating its antisense pairing with CDK4 and decreasing retinoblastoma protein phosphorylation in human cervical cancer. Therefore, the results of the present study suggest that TSPAN31 may serve as a potential molecular target for the development of novel anti-cancer agents. SIGNIFICANCE OF THE
Natural antisense transcripts are widely found in the genome and play an important role in the growth and development of cells. TSPAN31 is natural antisense transcript, and CDK4 is an important gene in the regulation of the cell cycle. Therefore, TSPAN31 and CDK4 have great significance in the study of tumour therapeutic targets.
This article was published in the following journal.
Name: Cell biochemistry and function
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Morphological abnormalities of the cervical EPITHELIUM, usually revealed in PAP SMEAR, which do not meet the criteria for squamous CERVICAL INTRAEPITHELIAL NEOPLASIA or SQUAMOUS CELL CARCINOMAS of the CERVIX . It may be a sign of infection with certain types of human papillomavirus (HPV).or sign of a benign (not cancer) growth, such as a cyst or polyp or, in menopausal women, of low hormone levels. More testing, such as HPV test, may be needed.
Retrovirus-associated DNA sequences (erbB) originally isolated from, or related to, the avian erythroblastosis virus (AEV). These genes code for the epidermal growth factor receptor (EGFR) family of receptors which is important in the control of normal cell proliferation and in the pathogenesis of human cancer. The genes include erbB-1 (GENES, ERBB-1), erbB-2 (GENES, ERBB-2), and erbB-3, all of which show abnormalities of expression in various human neoplasms.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
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The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.
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