Tumor Suppressor miRNA in Cancer Cells and the Tumor Microenvironment: Mechanism of Deregulation and Clinical Implications

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that have been identified as important posttranscriptional regulators of gene expression. miRNAs production is controlled at multiple levels, including transcriptional and posttranscriptional regulation. Extensive profiling studies have shown that the regulation of mature miRNAs expression plays a causal role in cancer development and progression. miRNAs have been identified to act as tumor suppressors (TS) or as oncogenes based on their modulating effect on the expression of their target genes. Upregulation of oncogenic miRNAs blocks TS genes and leads to tumor formation. In contrast, downregulation of miRNAs with TS function increases the translation of oncogenes. Several miRNAs exhibiting TS properties have been studied. In this review we focus on recent studies on the role of TS miRNAs in cancer cells and the tumor microenvironment (TME). Furthermore, we discuss how TS miRNA impacts the aggressiveness of cancer cells, with focus of the mechanism that regulate its expression. The study of the mechanisms of miRNA regulation in cancer cells and the TME may paved the way to understand its critical role in the development and progression of cancer and is likely to have important clinical implications in a near future. Finally, the potential roles of miRNAs as specific biomarkers for the diagnosis and the prognosis of cancer and the replacement of tumor suppressive miRNAs using miRNA mimics could be promising approaches for cancer therapy.

MicroRNA-21 Expression as a Prognostic Biomarker in Oral Cancer: Systematic Review and Meta-Analysis

“…The main genetic alterations affecting carcinogenesis involve changes in tumor suppressors (APC, p53 BRCA2, PTCH, NF1, VHL, Rb BCL2, SWI/SNF, p16, CD95, ST5, YPEL3, ST7, and ST14) and oncogenes (Ras, jun, fas, erbA, abl, raf, gsp, sis, erbB, and fms) in addition the onset and progression of oral cancer involve changes of DNA methylation, histone modifications, and non-coding alterations of RNA, including microRNAs (miRNA) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

The Functional Mechanism of MicroRNA in Oral Lichen Planus

“…MiRNAs are ncRNAs with a length of 20–25 nucleotides that influence gene expression after transcription. 29 The majority of mature miRNA sequences are found in ncRNA introns, ncRNA exons, and pre-mRNA introns, and miRNAs are processed from protein-coding gene introns or RNA polymerase II-specific transcripts of separate genes. 30 , 31 Increasing evidence demonstrates that miRNAs act as key regulators of development and cellular homeostasis by controlling a variety of biological processes.…”

miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy

“…One mRNA might be targeted by numerous related or unrelated miRNAs [ 33 , 34 ]. It has been reported that one miRNA complex can target almost two hundred genes of variable functions [ 35 ]. About 60% of human genes can be targeted by these miRNAs, once their corresponding mRNAs targets are regulated by miRNA, influencing various pathways, including cancer [ 36 , 37 ].…”