MicroRNA-141 is downregulated in human renal cell carcinoma and regulates cell survival by targeting CDC25B

Abstract

Background/objectiveMicroRNAs (miRNAs) are small noncoding RNAs (ribonucleic acids), approximately 22 nucleotides in length, that function as regulators of gene expression. Dysregulation of miRNAs has been associated with the initiation and progression of oncogenesis in humans. The cell division cycle (CDC)25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation.MethodsUsing miRNA target prediction software, we found that miR-141 could target the 3′ untranslated region (3′UTR) sequence of CDC25B. To shed light on the role of miR-141 in renal cell carcinogenesis, the expression of miR-141 was examined by real-time polymerase chain reaction (RT-PCR) in renal cell carcinoma and normal tissues. The impact of miR-141 re-expression on 769-P cells was analyzed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-forming assay. A luciferase reporter assay was applied to prove the functionality of the miR-141 binding site.ResultsmiR-141 is significantly downregulated in renal cell carcinoma. miR-141 re-expression suppressed cell growth in 769-P cells. Luciferase expression from a reporter vector containing the CDC25B-3′UTR was decreased when this construct was transfected with miR-141 in 769-P cells. The overexpression of miR-141 suppressed the endogenous CDC25B protein level in 769-P cells.ConclusionFor the first time, we demonstrated that CDC25B is a direct target of miR-141 in renal cell carcinoma. The transcriptional loss of miR-141 and the resultant increase in CDC25B expression facilitates increased genomic instability at an early stage of renal cell carcinoma development.

Prognostic value of meta-signature miRNAs in renal cell carcinoma: an integrated miRNA expression profiling analysis

“…High-throughput technologies have been employed to identify differences in miRNA expression levels between tumor and normal tissues. Recently, increasing number of miRNA profiling datasets have grown rapidly, however, recent miRNA expression profiling datasets showed inconsistent results between the studies due to different technological platforms and small sample size application 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 . Considering inconsistent annotation and ongoing discovery of new miRNAs, different detection methods used by different technological platforms, various methods for data processing and analysis, we are trying to find a meaningful way in which to combine the results of several individual studies in order to increase the statistical power.…”

MicroRNA-141-5p Acts as a Tumor Suppressor via Targeting RAB32 in Chronic Myeloid Leukemia

“…MiR-141 is widely expressed in many human malignant tumors and is highly expressed in tumors such as ovarian cancer (Mateescu et al, 2011), NSCLC tissues (Mei et al, 2014), nasopharyngeal cancer (Zhang et al, 2010), prostate cancer (Seol et al, 1996), thyroid papillary cancer (van Bokhoven et al, 2003), and colorectal cancer (Hu et al, 2010), but has low level in nasopharyngeal carcinoma (Li M. et al, 2019), hepatocellular carcinoma (Hou et al, 2019), esophageal cancer (Imanaka et al, 2011), non-small cell lung cancer , breast cancer (Finlay-Schultz et al, 2015), and renal cell carcinoma (Yu et al, 2013). These results indicate that miR-141 plays a dual role of an oncogene or tumor suppressor by regulating target genes, which provides a new alternative for treatment in the course of different tumorigeneses and developments.…”

microRNA-184 functions as tumor suppressor in renal cell carcinoma

“…Researchers observed that miRNAs post-transcriptionally regulated the expression of more than 30% of protein coding genes by translational repression, which also regulated the expression of several putative target genes by binding to a complementary sequence predominantly in their untranslated region. However, the bindings are not always completely complementary, particularly in mammals ( 29 , 30 ). Moreover, further research should be conducted to determine the roles and target genes of miR-184 in renal cell carcinoma.…”