Abstract 3075: miRNA-10a enhances invasiveness via suppression of HDAC5 in lung cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.3075-3075
• Main Authors: Hsu, Pin-Yen, Ho, Bing-Ching, Cheng, Chiou-Ling, Chen, Hsuan-Yu, Yu, Sung-Liang, Huang, Guan-Tarn
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-3075

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Metastasis, the spread process of cancer cells from a primary tumor to seed secondary tumors in distant sites, is one of the big challenges in cancer treatment today. For most patients, when the cancer is detected, metastasis has already occurred. The growing evidences implied that miRNAs play an important role in developmental lineage and different states of cancers as well as cancer invasion. In this study, we would like to establish a metastasis-based prognostic miRNA signature. First, 16 lung adenocarcinoma cells were divided into the high or low-invasive group. The miRNAs whose expression correlated with invasion were identified. Next, we investigated whether the expressions of identified miRNAs are correlated to patients’ survival. Quantitative RT-PCR results showed that the expression of miR-10a* is significantly correlated to the five-year survival in 98 lung adenocarcinoma patients. The inhibition of miR-10a* attenuated the invasion abilities of the highly invasive lung cancer cells. Moreover, we investigated the underlying regulation of miR-10a*. We found that miR-10a* negatively regulated Histone deacetylase 5 (HDAC5) was assayed by Western Blot, RT-PCR and luciferase reporter assay. These evidences suggested that HDAC5 is a direct target of miR-10a*. Besides, inhibition of HDAC5 promoted invasive ability. RNAs derived from two paired groups (pre-miR-10a* and pre-NC; sh-HDAC5 and sh-LacZ) were assayed by microarray and pathway analysis. The analysis result of MetaCore implied that miR-10a* trigger TGF-beta signalings. RT-PCR and Western Blot were utilized to validate the differentially altered expression of certain genes in miR-10a*-mediated pathways. The rescue effect of HDAC5 expression on miR-10a*-mediated phenotypic changes is also evaluated to elucidate the importance of HDAC5 in miR-10a*-mediated invasive ability. Our findings indicated that miR-10a* may play an oncogenic miRNA role in lung cancer. Citation Format: Pin-Yen Hsu, Bing-Ching Ho, Chiou-Ling Cheng, Hsuan-Yu Chen, Sung-Liang Yu, Guan-Tarn Huang. miRNA-10a* enhances invasiveness via suppression of HDAC5 in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3075. doi:10.1158/1538-7445.AM2015-3075