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MiR-133b, a particular member of myomiRs, coming into playing its unique pathological role in human cancer.

ABSTRACT: MicroRNAs, a family of single-stranded and non-coding RNAs, play a crucial role in regulating gene expression at posttranscriptional level, by which it can mediate various types of physiological and pathological process in normal developmental progress and human disease, including cancer. The microRNA-133b originally defined as canonical muscle-specific microRNAs considering their function to the development and health of mammalian skeletal and cardiac muscles, but new findings coming from our group and others revealed that miR-133b have frequently abnormal expression in various kinds of human cancer and its complex complicated regulatory networks affects the tumorigenicity and development of malignant tumors. Very few existing reviews on miR-133b, until now, are principally about its role in homologous cluster (miR-1, -133 and -206s), however, most of constantly emerging new researches now are focused mainly on one of them, so In this article, to highlight the unique pathological role of miR-133b playing in tumor, we conduct a review to summarize the current understanding about one of the muscle-specific microRNAs, namely miR-133b, acting in human cancer. The review focused on the following four aspects: the overview of miR-133b, the target genes of miR-133b involved in human cancer, the expression of miR-133b and regulatory mechanisms leading to abnormal expression of miR-133b.

SUBMITTER: Li D

PROVIDER: S-EPMC5564843 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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miR-133b, a particular member of myomiRs, coming into playing its unique pathological role in human cancer.

Li Daojiang D Xia Lu L Chen Miao M Lin Changwei C Wu Hao H Zhang Yi Y Pan Songqing S Li Xiaorong X

Oncotarget 20170701 30

MicroRNAs, a family of single-stranded and non-coding RNAs, play a crucial role in regulating gene expression at posttranscriptional level, by which it can mediate various types of physiological and pathological process in normal developmental progress and human disease, including cancer. The microRNA-133b originally defined as canonical muscle-specific microRNAs considering their function to the development and health of mammalian skeletal and cardiac muscles, but new findings coming from our g ...[more]

PMID: 28422730

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Project description:BackgroundNucleoporins mediate nucleocytoplasmic exchange of macromolecules and several have been assigned active mitotic functions. Nucleoporins can participate in various mitotic functions like spindle assembly, kinetochore organisation and chromosome segregation- important for genome integrity. Pathways to genome integrity are frequently deregulated in cancer and many are regulated in part by microRNAs. Indeed, altered levels of numerous microRNAs have frequently been associated with tumorigenesis. Here, we unveil a microRNA-mediated regulation of the nucleoporin Nup214 and its downstream effect on genome integrity.MethodsDatabases/bioinformatic tools such as miRBase, Oncomine and RNAhybrid predicted Nup214 as a miR-133b target. To validate this, we used luciferase reporter assays, Real-Time PCR and immuno-blotting. Flow cytometry and immuno-blots of mitotic markers were used to analyse cell cycle pattern upon thymidine synchronization and miR-133b treatment. Mitotic indices and chromosomal abnormalities were assessed by immuno-fluorescence for FITC-tagged phospho-H3 as well as video-microscopy for GFP-tagged histone H4. Annexin V/propidium iodide staining, caspase3/PARP cleavage and colony formation assays were done to investigate cell death upon either miR-133b transfection or NUP214 knockdown by siRNA. UPCI:SCC084, HCT116, HeLa-H4-pEGFP and HEK293 (human oral squamous cell carcinoma, colorectal, cervical carcinomas and embryonic kidney cell lines, respectively) were used. miR-133b and NUP214 expressions were validated in cancer cell lines and tissues by Real-Time PCR.ResultsExamination of head and neck tumour tissues and cancer cell lines revealed that Nup214 and miR-133b expressions are negatively correlated. In vitro, Nup214 was significantly downregulated by ectopic miR-133b. This downregulation elevated mitotic indices and delayed degradation of mitotic marker proteins cyclinB1 and cyclinA and dephosphorylation of H3. Moreover, this mitotic delay enhanced chromosomal abnormalities and apoptosis.ConclusionsWe have identified NUP214, a member of the massive nuclear pore complex, as a novel miR-133b target. Thus, we have shown a hitherto unknown microRNA regulation of mitosis mediated by a member of the nucleoporin family. Based on observations, we also raise some hypotheses regarding transport-dependent/independent functions of Nup214 in this study. Our results hence attempt to explain why miR-133b is generally downregulated in tumours and lay out the potential for Nup214 as a therapeutic target in the treatment of cancer.

Project description:The present study aimed to investigate the expression levels and clinical significance of microRNA (miR)-203 and miR-133b in laryngeal carcinoma. A total of 154 patients with laryngeal carcinoma (research group) along with 100 healthy individuals (control group) were enrolled in the study. The patients were admitted to Yidu Central Hospital of Weifang (Weifang, China) from February 2016 to October 2018. Fasting venous blood (5 ml) was extracted from all subjects to determine the expression levels of serum miR-203 and miR-133b by reverse transcription-quantitative polymerase chain reaction (PCR) and to compare them among patients with different pathological characteristics. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic values of miR-203 and miR-133b for laryngeal carcinoma. The research group showed significantly lower expression levels of miR-203 and miR-133b than the control group (P<0.05). According to ROC curve analysis, when the cut-off value was 0.659, the sensitivity and specificity of miR-203 in diagnosing laryngeal carcinoma were 60.00 and 90.26%, respectively, whereas when the cut-off value was 1.398, the sensitivity and specificity of miR-133b were 55.00 and 87.66%, respectively. The sensitivity and specificity of the joint detection were 70.00 and 83.77%, respectively, when the cut-off value was 0.416. In the research group, miR-203 was expressed significantly different in patients with different pathological stages and tumor types (P<0.050). The expression of miR-133b varied significantly in patients with different pathological stages, differentiation degrees and lymph node metastasis (P<0.050). In conclusion, miR-203 and miR-133b were expressed at low levels in patients with laryngeal carcinoma. The expression of miR-203 was related to tumor-node-metastasis (TNM) stage and tumor type, whereas the expression of miR-133b was related to TNM stage, differentiation degree, as well as lymph node metastasis. Joint detection of miR-203 and miR-133b is expected to be an excellent marker for the diagnosis and treatment of laryngeal carcinoma.

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MiR-133b, a particular member of myomiRs, coming into playing its unique pathological role in human cancer.

Publications

miR-133b, a particular member of myomiRs, coming into playing its unique pathological role in human cancer.

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