Bibliographic Details
| Title: |
Factor VII-Induced MicroRNA-135a Inhibits Autophagy and Is Associated with Poor Prognosis in Hepatocellular Carcinoma |
| Authors: |
Kuang-Tzu Huang, I-Ying Kuo, Ming-Chao Tsai, Chun-Hsien Wu, Li-Wen Hsu, Li-Yu Chen, Chao-Pin Kung, Yu-Fan Cheng, Shigeru Goto, Yu-Wei Chou, Chao-Long Chen, Chih-Che Lin, Kuang-Den Chen |
| Source: |
Molecular Therapy: Nucleic Acids, Vol 9, Iss C, Pp 274-283 (2017) |
| Publisher Information: |
Elsevier, 2017. |
| Publication Year: |
2017 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
hepatocellular carcinoma, FVII, miR-135a, autophagy, Atg14, recurrence, microvascular invasion, survival, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies worldwide. Treatment outcomes remain poor mainly due to lack of good diagnostic/prognostic markers and limited therapeutic strategies. We previously characterized aberrant activation of the TF/FVII/PAR2 pathway, which subsequently results in decreased autophagy, as a crucial event in malignant progression of HCC. Here, we identified miR-135a as a highly upregulated miRNA in HCC in response to TF/FVII/PAR2 activation. Analyzing 103 HCC patient specimens, we confirmed that miR-135a was frequently elevated in HCC tissues with higher FVII expression compared to adjacent non-cancerous counterparts. Increased miR-135a levels in HCC were also associated with tumor staging, recurrence, microvascular invasion, and decreased disease-free survival. We subsequently identified Atg14, a key component that regulates the formation of autophagosome as a direct target of miR-135a. Ectopic expression of miR-135a suppressed Atg14 levels and inhibited the autophagic processes. Our results indicate strong positive correlations between miR-135a levels and malignant behaviors in HCC patients and also suggest novel functions of miR-135a in regulation of autophagy, which could be useful as a potential target for prognostic and therapeutic uses. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2162-2531 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2162253117302639; https://doaj.org/toc/2162-2531 |
| DOI: |
10.1016/j.omtn.2017.10.002 |
| Access URL: |
https://doaj.org/article/48e5dc56d831470086092efeab740567 |
| Accession Number: |
edsdoj.48e5dc56d831470086092efeab740567 |
| Database: |
Directory of Open Access Journals |
