406935

MIR143

microRNA 143;MIR143;microRNA 143

hsa-mir-143

5q32

ncRNA

OBJECTIVE: This study is to investigate the role of miR-143 expression in cervical squamous cell carcinoma (SCC). METHODS: The expression level of miR-143 was examined by quantitative real-time PCR. Human papillomavirus (HPV) genotype was detected by HPV genotype detection kit. The expression level of bcl-2 was detected by immunohistochemistry. RESULTS: The positive rate of HPV was 78% in the patients of cervical SCC. The most prevalent genotype was HPV16, with a positive rate of 42%. The expression level of miR-143 was significantly lower in the cervical SCC tissues than that in the normal cervical tissues (Z=-2.180, P=0.029). Down-regulated miR-143 expression was associated with tumor size, lymph node metastasis and HPV16 infection in cervical cancer patients. No significant associations were found between the expression levels of miR-143 and age, clinical stage, differentiation or lymph vascular space invasion. And, in cervical SCC patients after treatment with Taxol chemotherapy, the expression level of miR-143 was higher and the positive expression of bcl-2 protein was lower. However, the differences in expression changes of miR-143 and bcl-2 were not statistically significant (miR-143, Z=-0.763, P=0.446; bcl-2 protein, chi2=2.277, P=0.131). CONCLUSION: Down-regulated miR-143 is related with tumor size, lymph node metastasis and HPV16 infection in cervical SCC, but miR-143 does not participate in the Taxol sensitivity response. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1401279451112150.

In spite of the undisputed importance of altered expression patterns of microRNAs (miRNAs) in various cancers, there is little information on the clinicopathologic significance of cancer-related miRNAs (MIR21, MIR143, MIR144, MIR145, and MIR205) in esophageal squamous cell carcinoma (ESCC). We examined the expression levels of the precursor and mature miRNA genes in ESCC using real-time polymerase chain reaction (PCR). We also investigated the mRNA expression levels of processing elements (RNASEN, DGCR8, and DICER1) that participate in miRNA-biogenesis pathway. Furthermore, we analyzed the relationships between the expression levels of these five miRNAs and the clinicopathologic parameters of ESCC patients. The expression levels of mature MIR21 and mature MIR145 were higher in ESCC than those in normal epithelium (P < 0.05). The mature/pre ratio of MIR21 in ESCC was higher than that in normal epithelium (P < 0.05). With regard to miRNA-processing elements, the expression level of RNASEN was higher in ESCC than in normal epithelium (P < 0.05). Furthermore, altered expression of these miRNAs was related to the clinicopathologic features of ESCC patients. The high expression of mature MIR21 and mature MIR205 was associated with lymph node positivity in ESCC patients (P < 0.05). The high levels of expression of mature MIR143 and mature MIR145 were associated with recurrence of metastasis in ESCC patients (P < 0.05). The findings may imply that miRNA biogenesis is aberrantly accelerated in ESCC. Analysis of the expression levels of miRNAs should provide useful information for evaluation of the staging, prognosis, and treatment of ESCC patients.

It is increasingly clear that hepatocellular carcinoma (HCC) has a distinct microRNA (miRNA) expression profile that is involved in malignancy; however, little is known about how functional miRNA modulates the metastasis of hepatitis B virus (HBV)-related HCC (HBV-HCC). In the present study, we demonstrate that the levels of miRNA-143 (miR-143) are dramatically increased in metastatic HBV-HCC of both p21-HBx transgenic mice and HCC patients. Moreover, we show that overexpression of this miRNA is transcribed by nuclear factor kappa B (NF-kappaB) and favors liver tumor cell invasive and metastatic behavior. Intratumoral administration of miR-143 shows that high levels of miR-143 can significantly promote HCC metastasis in an athymic nude mouse model. An in vivo study that used p21-HBx transgenic mice also showed that local liver metastasis and distant lung metastasis are significantly inhibited by blocking miR-143. Additionally, fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as the direct and functional target of miR-143 both in vivo and in vitro. CONCLUSION: Up-regulation of miR-143 expression transcribed by NF-kappaB in HBV-HCC promotes cancer cell invasion/migration and tumor metastasis by repression of FNDC3B expression. The present study provides a better understanding of the specificity of the biological behavior and thus may be helpful in developing an effective treatment against HBV-HCC.

Pancreatic cancer is characterized by early metastasis and high mortality. In this study, the role of miR-143 in invasion and metastasis was investigated in pancreatic cancer cells. miR-143 expression was established by an adenovirus-carried miR-143 expression cassette. mRNA and protein levels of gene expression were examined by RT-PCR and Western blot assay, respectively. Rho GTPases activity was measured by the pull down assay. The role of miR-143 in migration and invasion of Panc-1 cells was tested in vitro. The antimetastatic effect of miR-143 was tested in a liver metastasis model, while its antitumor growth effect was tested in a xenograft Panc-1 tumor model. Results demonstrated that ARHGEF1 (GEF1), ARHGEF2 (GEF2), and K-RAS genes are the targets of miR-143. miR-143 expression significantly decreased mRNA and protein levels of GEF1, GEF2, and K-RAS genes; lowered the constitutive activities of RhoA, Rac1, and Cdc42 GTPases; decreased the protein levels of MMP-2 and MMP-9; but significantly increased the protein level of E-cadherin. miR-143 expression also significantly inhibited the migration and invasion of Panc-1 cells in vitro, liver metastasis, and xenograft tumor growth in vivo. Our study suggested that miR-143 plays a central role in the invasion and metastasis of pancreatic cancer and miR-143 is a potential target for pancreatic cancer therapy.

The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone. MicroRNAs (miRNAs) play a crucial role in many tumor metastases. The importance of miRNAs in bone metastasis of PCa has not been elucidated to date. We investigated whether the expression of certain miRNAs was associated with bone metastasis of PCa. We examined the miRNA expression profiles of 6 primary and 7 bone metastatic PCa samples by miRNA microarray analysis. The expression of 5 miRNAs significantly decreased in bone metastasis compared with primary PCa, including miRs-508-5p, -145, -143, -33a and -100. We further examined other samples of 16 primary PCa and 13 bone metastases using real-time PCR analysis. The expressions of miRs-143 and -145 were verified to down-regulate significantly in metastasis samples. By investigating relationship of the levels of miRs-143 and -145 with clinicopathological features of PCa patients, we found down-regulations of miRs-143 and -145 were negatively correlated to bone metastasis, the Gleason score and level of free PSA in primary PCa. Over-expression miR-143 and -145 by retrovirus transfection reduced the ability of migration and invasion in vitro, and tumor development and bone invasion in vivo of PC-3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. Their upregulation also increased E-cadherin expression and reduced fibronectin expression of PC-3 cells which revealed a less invasive morphologic phenotype. These findings indicate that miRs-143 and -145 are associated with bone metastasis of PCa and suggest that they may play important roles in the bone metastasis and be involved in the regulation of EMT Both of them may also be clinically used as novel biomarkers in discriminating different stages of human PCa and predicting bone metastasis.

Emerging evidence demonstrates that cancer stem cells (CSCs) are the critical drivers of tumor progression and metastasis. The microRNAs (miRNAs) may play a crucial role in repressing/promoting metastasis of cancer by regulating CSCs. A previous study showed that miR-143 and miR-145 play an important role in regulating bone metastasis of prostate cancer (PCa), but the exact mechanism of regulation of bone metastasis of PCa is not fully understood. In this study, we found that overexpression of miR-143 and miR-145 inhibited the cell viability and colony formation of PC-3 cells from PCa bone metastasis. Furthermore, miR-143 and miR-145 suppressed tumor sphere formation and expression of CSC markers and 'stemness' factors including CD133, CD44, Oct4, c-Myc and Klf4 in PC-3 cells. The study further found that miR-143 and miR-145 inhibit bone invasion and tumorigenicity of PC-3 cells in vivo. Collectively, these findings demonstrate that miR-143 and miR-145 inhibit CSC properties of PC-3 cells and suggest that miR-143 and miR-145 may play a significant role in the bone metastasis progression of PCa by regulating CSC characteristics.