Diverse microRNAs with convergent functions regulate tumorigenesis

Abstract

Abstract. MicroRNAs (miRNAs) regulate several biological processes, including tumorigenesis. In order to comprehend the roles of miRNAs in cancer, various screens were performed to investigate the changes in the expression levels of miRNAs that occur in different types of cancer. The present review focuses on the results of five recent screens, whereby a number of overlapping miRNAs were identified to be downregulated or differentially regulated, whereas no miRNAs were observed to be frequently upregulated. Furthermore, the majority of the miRNAs that were common to >1 screen were involved in signaling networks, including wingless-related integration site, receptor tyrosine kinase and transforming growth factor-β, or in cell cycle checkpoint control. The present review will discuss the aforementioned miRNAs implicated in cell cycle checkpoint control and signaling networks. IntroductionMicroRNAs (miRNAs) are small non-coding RNAs of 21-25 nucleotides in length that control gene expression via post-transcriptional regulation (1). Contrasting with the maturation process of normal coding RNAs, the miRNA genes are initially transcribed by RNA polymerase II into a primary transcript in the nucleus, where the hairpin structure is processed into precursor miRNA by a microprocessing complex that includes Drosha and DiGeorge syndrome chromosomal (or critical) region 8 (DGCR8) (1). Subsequently, the ~70 nucleotide-long precursor miRNA is exported into the cytoplasm, where it undergoes secondary processing by Dicer, and one strand of the hairpin is then incorporated into a ribonucleoprotein complex known as miRNA-induced silencing complex (1). Once matured, a single miRNA may target miscellaneous messenger RNAs (mRNAs), and an individual mRNA may be regulated by various miRNAs (1). miRNAs have significant roles during stem cell maintenance and differentiation (2). In addition, they have frequently been used as markers for certain types of cancer cells, by comparing the measured levels of known miRNAs with those present in their wild-type counterparts (2,3). Screens investigating differential expression of miRNAs in various cancer cell populations have been previously performed. The present review will focus on the results of five screens conducted in the past recent years, which investigated prostate cancer (3), neuroblastoma (4), pancreatic cancer (5), chronic myeloid leukemia (CML) (6) and osteosarcoma cells (7). Specifically, Liu et al (3) used three prostate cancer metastatic cell lines, namely LAPC9, LAPC4 and Du145 [bone cluster of differentiation (CD)44 + /CD44 -subpopulation sorting based on LAPC9, LAPC4 and Du145 cell lines; side population (SP)/non-SP sorting based on LAPC9 cell line; and CD133 + /CD133 -subpopulation sorting based on LAPC4 cell line], and compared the expression levels of miscellaneous miRNAs (with vs. without markers) in these cells. Following testing for 324 DGCR8 miRNAs by reverse transcription-quantitative polymerase chain reaction, 137 miRNAs were identified to be expressed in the three ce...

Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?

“…miRNA duplex structures are separated by helicase and two single-stranded RNA molecules, termed guide strand and passenger strand, which were generated, based on their 5’ to 3’ complementarity. During this selection process, passenger strand is degraded, while the guide strand is incorporated into the RNA-induced silencing complex (RISC) and functions as a mature miRNA [29–31]. If mature miRNA is produced from a 5’ strand, its nomenclature is miRNA-5p, and if it is generated from a 3’ strand, it is represented as miRNA-3p (http://atlasgeneticsoncology.org).…”

miRNAs and Stem Cells as Promising Diagnostic and Therapeutic Targets for Alzheimer’s Disease

“…After cleavage, guide strand is incorporated into RNAinduced silencing complex (RISC) while passenger strand is degraded. miRNAs form the RISC complex with Argonaute2 (Ago2) proteins which induces the post-transcriptional regulation of gene expression through two different mechanisms either by translation inhibition or mRNA degradation according to the complementarity between the miRNA and its target mRNA [128,131,132]. MiRNAs that bind totally to the complementary areas (3 UTR) of their target mRNA stimulate its degradation through de-adenylation, cap removal, and exonucleolytic digestion.…”