Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastasis is one of the causes of cancer death. Functions and mechanisms of microRNAs (miRNAs) involved in hepatocellular carcinoma (HCC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in MHCC-97L, MHCC-97H and HCC-LM3 cells with gradually increasing metastatic potential to disclose crucial miRNAs involved in HCC metastasis. miR-192 expression decreased and negatively correlated with vascular invasion in HCC specimens. Gain and loss of function studies revealed that miR-192 significantly suppressed metastasis of HCC cells in vitro and in vivo. Solute carrier family 39 member 6 (SLC39A6) was identified as a direct and functional target of miR-192. In addition, SLC39A6 negatively correlated with miR-192 in HCC samples and promoted HCC cell migration and invasion. Moreover, miR-192 decreased SLC39A6 expression, subsequently downregulating SNAIL and upregulating E-cadherin expression. Suppression of migration and invasion caused by miR-192 overexpression was alleviated by exogenous Snail expression. Intriguingly, lower miR-192 expression and higher SLC39A6 expression significantly contributed to poorer outcomes in HCC patients. Multivariate analysis indicated that miR-192 was an independent and significant predictor of HCC patient overall survival. In conclusion, we newly determined that miR-192 targeted the SLC39A6/SNAIL pathway to reduce tumor metastasis in HCC cells. This axis provided insights into the mechanism underlying miRNA regulation of HCC metastasis and a novel therapeutic target for HCC treatment.
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PMID:miR-192, a prognostic indicator, targets the SLC39A6/SNAIL pathway to reduce tumor metastasis in human hepatocellular carcinoma. 2668 41

Metastasis is the most common cause of mortality for non-small cell lung cancer (NSCLC). PTCH1, a receptor of Hedgehog (Hh) pathway, is reported to suppress cell proliferation. Interestingly, our previous study showed PTCH1 silencing promoted cell proliferation but inhibited cell migration and invasion of NSCLC cells. However, the precise mechanisms of PTCH1 regulating NSCLC metastasis remain unclear. PTCH1 has multiple splicing variants, which all share the same 3'UTR sequence, meanwhile, emerging studies have shown competing endogenous RNAs (ceRNAs) play important roles in regulating cancer progression. Therefore, we hypothesized the functions of PTCH1-3'UTR in NSCLC in present study to reveal its role as a ceRNA. Here, we find overexpression of PTCH1-3'UTR promotes cell migration, invasion and adhesion, but does not affect cell proliferation in NSCLC cells. By combining weighted correlation network analysis (WGCNA) analysis and experimental validation, we reported PTCH1-3'UTR acted as a sponge to absorb miR-101-3p and promoted SLC39A6 expression. Moreover, we observed low expression of miR-101-3p and PTCH1 and high SLC39A6 levels were positively correlated with NSCLC progression. Therefore, our results help to understand the function of PTCH1 in NSCLC tumorigenesis and provide novel insights for the prevention of NSCLC metastasis.
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PMID:Co-expression analysis revealed PTCH1-3'UTR promoted cell migration and invasion by activating miR-101-3p/SLC39A6 axis in non-small cell lung cancer: implicating the novel function of PTCH1. 2943 42