Abstract 515: G12 overexpression in hepatocellular carcinoma promotes epithelial-mesenchymal transition through microRNAs deregulation
| Autor: | Yoon Mee Yang, Chang H. Lee, Sung Hoon Kim, Kang M. Kim, Sang Geon Kim, Jihyun An, Tae Hyun Kim, Chan Gyu Lee, Seung Jin Lee, Sejin Hwang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty biology business.industry Cancer Cell migration medicine.disease medicine.disease_cause Oncology Tumor progression Hepatocellular carcinoma microRNA Cancer research biology.protein medicine Mdm2 Epithelial–mesenchymal transition business Carcinogenesis |
| Zdroj: | Cancer Research. 74:515-515 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2014-515 |
| Popis: | Hepatocellular carcinoma (HCC) has a poor prognosis due to its aggressive nature. Ligand activation of G-protein coupled receptor with enhanced G-protein activity may contribute to tumorigenesis and tumor progression in microenvironments. Here, we report the overexpression of Gα12 in HCC and its effect on deregulation of microRNAs in association with epithelial-mesenchymal transition. Gα12 expression levels were higher in human HCC than surrounding normal tissue. Array analyses using Huh7 cells stably transfected with an active mutant of Gα12 (Gα12QL) enabled us to extract down-regulated microRNAs. Of them, decreases of miR-200b/a, -192 and -215 contributed to ZEB induction through the up-regulation of MDM2. Transfection with miR-200b, -192 or miR-215 mimic antagonized HCC cell migration and invasion facilitated by Gα12QL. In tumor xenograft studies, sustained knockdown of Gα12 decreased the overall growth rate and average volume of tumors derived from SK-Hep1, a mesenchymal liver tumor cell line. In human HCC samples, levels of the identified microRNAs were all decreased, and correlated with the induction of mesenchymal markers. Moreover, decreases of the miRNAs discriminated microvascular invasion versus non-microvascular invasion of HCC. Conclusion: Increase of Gα12 in HCC deregulates a set of miRNAs promoting epithelial-mesenchymal transition of HCC and may be responsible for tumor microvascular invasion, implying that Gα12 signaling and the downstream mediators may be utilized as therapeutic targets and/or prognostic markers. Citation Format: Sang Geon Kim, Yoon Mee Yang, Tae Hyun Kim, Chan Gyu Lee, Jihyun An, Sung Hoon Kim, Chang Ho Lee, Sejin Hwang, Seung Jin Lee, Kang Mo Kim. G12 overexpression in hepatocellular carcinoma promotes epithelial-mesenchymal transition through microRNAs deregulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 515. doi:10.1158/1538-7445.AM2014-515 |
| Databáze: | OpenAIRE |
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