Lung cancer cells expressing a shortened CDK16 3′UTR escape senescence through impaired miR‐485‐5p targeting
| العنوان: | Lung cancer cells expressing a shortened CDK16 3′UTR escape senescence through impaired miR‐485‐5p targeting |
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| المؤلفون: | Leihuan Huang, Ting Ni, Baiyun Xie, Zhaozhao Zhao, Gang Wei, Qi Jia |
| المصدر: | Molecular Oncology. 16:1347-1364 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Senescence, Untranslated region, Cancer Research, Gene knockdown, Lung Neoplasms, biology, Three prime untranslated region, Genes, myc, Cancer, General Medicine, medicine.disease, Cyclin-Dependent Kinases, MicroRNAs, Oncology, Cyclin-dependent kinase, Cell Line, Tumor, microRNA, Cancer cell, Genetics, biology.protein, medicine, Cancer research, Humans, Molecular Medicine, 3' Untranslated Regions |
| الوصف: | Inducing senescence in cancer cells is an emerging strategy for cancer therapy. The dysregulation and mutation of genes encoding cyclin-dependent kinases (CDKs) have been implicated in various human cancers. However, whether CDK can induce cancer cell senescence remains poorly understood. We observed that CDK16 expression was high in multiple cancer types, including lung cancer, whereas various replicative senescence models displayed low CDK16 expression. CDK16 knockdown caused senescence-associated phenotypes in lung cancer cell lines. Interestingly, the CDK16 3' untranslated region (UTR) was shortened in cancer and lengthened in senescence models, which was regulated by alternative polyadenylation (APA). The longer 3'UTR [using the distal polyA (pA) site] generated less protein than the shorter one (using the proximal pA site). Since microRNAs (miRNAs) usually bind to the 3'UTR of target genes to suppress their expression, we investigated whether miRNAs targeting the region between the shortened and longer 3'UTR are responsible for the reduced expression. We found that miR-485-5p targeted the 3'UTR between the distal and proximal pA site and caused senescence-associated phenotypes by reducing protein production from the longer CDK16 transcript. Of note, CDK16 knockdown led to a reduced expression of MYC proto-oncogene, bHLH transcription factor (MYC) and CD274 molecule (PD-L1), which in turn enhanced the tumor-suppressive effects of senescent cancer cells. The present study discovered that CDK16, whose expression is under the regulation of APA and miR-485-5p, is a potential target for pro-senescence lung cancer therapy. |
| تدمد: | 1878-0261 1574-7891 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef9e80cd1f63a183d92b324e395e67d9 https://doi.org/10.1002/1878-0261.13125 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ef9e80cd1f63a183d92b324e395e67d9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18780261 15747891 |
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