Abstract
Cell cycle is regulated by a number of proteins namely cyclin-dependent kinases (CDKs) and their associated cyclins which bind with and activate CDKs in a phase specific manner. Additionally, several transcription factors (TFs) such as E2F and p53 and numerous signaling pathways regulate cell cycle progression. Recent studies have accentuated the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of cell cycle. Both lncRNAs and miRNAs interact with TFs participating in the regulation of cell cycle transition. Dysregulation of cell cycle regulatory miRNAs and lncRNAs results in human disorders particularly cancers. Understanding the role of lncRNAs, miRNAs, and TFs in the regulation of cell cycle would pave the way for design of anticancer therapies which intervene with the cell cycle progression. In the current review, we describe the role of lncRNAs and miRNAs in the regulation of cell cycle and their association with human malignancies.
Highlights
Cell division has a fundamental role in the development multicellular organisms
Cell cycle is regulated by a number of proteins namely cyclin-dependent kinases (CDKs) and their associated cyclins which bind with and activate CDKs in a phase specific manner [2]
At the G1/S boundary, the complex constructed by cyclin E and CDK2 phosphorylates pRB and other proteins participating in the regulation of DNA replication to facilitate G1/S transition [8]
Summary
Cell division has a fundamental role in the development multicellular organisms. This process is accomplished through orderly sequences of happenings that together with each other make the “cell cycle”. Knockdown of NEAT1 by regulating miR-365/RGS20 axis could induce cell cycle arrest at the G0/G1 phase and inhibit cell proliferation and invasion. CASC11 by regulating cell cycle pathway via the miR-340-5p/CDK1 axis could promote GC cell proliferation, migration, and invasion. Overexpression of CDKN2B-AS1 via the miR-324-5p/ROCK1 axis by regulating cell cycle could promote LSCC cell proliferation According to their structural features, lncRNAs are categorized into different classes among them are intergenic, intronic and natural antisense lncRNAs [14]. The known oncogenic lncRNA MALAT1 regulates cell cycle progression at G1 phase since its knock down has resulted in cell cycle arrest at this step and enhanced expression of cell cycle inhibitors p53, p16, p21, and p27, while suppressing expression of cyclin A2 and CDC25A [18]. Knockdown of HOTTIP by blocking the Wnt/b-catenin pathway could inhibit cell proliferation and arrest cell cycle at the G1 phase. Higher expression of HOXD-AS1 was associated Higher expression of HOXD-AS1 was associated with histologic grade
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