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REVIEW: MicroRNAs in Cancer: From Gene Expression Regulation to the Metastatic Niche Reprogramming

Ekaterina V. Semina1,2,a*, Karina D. Rysenkova1,2, Konstantin E. Troyanovskiy2, Anna A. Shmakova1, and Kseniya A. Rubina2

1National Cardiology Research Center, Ministry of Health of the Russian Federation, 121552 Moscow, Russia

2Faculty of Fundamental Medicine, Lomonosov Moscow State University, 119192 Moscow, Russia

* To whom correspondence should be addressed.

Received March 11, 2021; Revised March 11, 2021; Accepted March 11, 2021
By 2003, the Human Genome project had been completed; however, it turned out that 97% of genome sequences did not encode proteins. The explanation came later when it was found the untranslated DNA contain sequences for short microRNAs (miRNAs) and long noncoding RNAs that did not produce any mRNAs or tRNAs, but instead were involved in the regulation of gene expression. Initially identified in the cytoplasm, miRNAs have been found in all cell compartments, where their functions are not limited to the degradation of target mRNAs. miRNAs that are secreted into the extracellular space as components of exosomes or as complexes with proteins, participate in morphogenesis, regeneration, oncogenesis, metastasis, and chemoresistance of tumor cells. miRNAs play a dual role in oncogenesis: on one hand, they act as oncogene suppressors; on the other hand, they function as oncogenes themselves and inactivate oncosuppressors, stimulate tumor neoangiogenesis, and mediate immunosuppressive processes in the tumors, The review presents current concepts of the miRNA biogenesis and their functions in the cytoplasm and nucleus with special focus on the noncanonical mechanisms of gene regulation by miRNAs and involvement of miRNAs in oncogenesis, as well as the authors’ opinion on the role of miRNAs in metastasis and formation of the premetastatic niche.
KEY WORDS: microRNA, RISC, Argonaute, microRNA biogenesis, microRNA functions in nucleus, exosomes, extracellular microRNA, oncogenesis, metastasis, metastatic niche

DOI: 10.1134/S0006297921070014