Next Article in Journal
Spironolactone, a Classic Potassium-Sparing Diuretic, Reduces Survivin Expression and Chemosensitizes Cancer Cells to Non-DNA-Damaging Anticancer Drugs
Next Article in Special Issue
Tumor Marker-Based Definition of the Transarterial Chemoembolization-Refractoriness in Intermediate-Stage Hepatocellular Carcinoma: A Multi-Cohort Study
Previous Article in Journal
Inherited Variants in BLM and the Risk and Clinical Characteristics of Breast Cancer
Previous Article in Special Issue
Sorafenib-Regorafenib Sequential Therapy in Japanese Patients with Unresectable Hepatocellular Carcinoma—Relative Dose Intensity and Post-Regorafenib Therapies in Real World Practice
Article

High Expression of MicroRNA-196a is Associated with Progression of Hepatocellular Carcinoma in Younger Patients

by 1,2,†, 3,†, 4,5, 6, 7,8,9, 10,11, 1,12,13, 6 and 1,6,9,*
1
Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan
2
Division of Gastroenterology and Hepatology, Department of Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan
3
School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan
4
Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan
5
Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan
6
Medical Research Department, Taipei Veterans General Hospital, Taipei 11217, Taiwan
7
Institute of Biomedical Informatics, National Yang-Ming University, Taipei 11221, Taiwan
8
Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei 11221, Taiwan
9
Cancer Progression Research Center, National Yang-Ming University, Taipei 11221, Taiwan
10
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
11
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
12
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City 33305, Taiwan
13
College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan
*
Author to whom correspondence should be addressed.
These authors have contributed equally to this work.
Cancers 2019, 11(10), 1549; https://doi.org/10.3390/cancers11101549
Received: 30 August 2019 / Revised: 10 October 2019 / Accepted: 11 October 2019 / Published: 13 October 2019
(This article belongs to the Special Issue Liver Cancer and Potential Therapeutic Targets)
MicroRNAs are small RNAs involved in various biological processes and cancer metastasis. miR-196a was associated with aggressive behaviors in several cancers. The role of miR-196a in hepatocellular carcinoma (HCC) metastasis remains unknown. This study aimed to examine the role of miR-196a in HCC progression. Expression of miR-196a was measured in 83 human HCC samples. The HCC patients with high miR-196a expression had younger ages, lower albumin levels, higher frequency with alpha-fetoprotein (AFP) levels ≥20 ng/mL, more macrovascular invasion, and non-early stages. Kaplan–Meier analysis showed that high miR-196a expression was associated with lower recurrence-free survival. Knockdown of miR-196a decreased transwell invasiveness, sphere formation, transendothelial invasion, and Slug, Twist, Oct4, and Sox2 expression, suppressed angiogenesis, and reduced sizes of xenotransplants and number of pulmonary metastasis. Down-regulation of miR-196a decreased Runx2 and osteopontin (OPN) levels. Knockdown of Runx2 in vitro resulted in comparable phenotypes with miR-196a down-regulation. Restoration of Runx2 in miR-196a-knockdown HCC reverted tumor phenotypes. This study showed that high expression of miR-196a is associated with HCC progression in a subset of younger patients. miR-196a mediates HCC progression via upregulation of Runx2, OPN, epithelial–mesenchymal transition (EMT) regulators, and stemness genes. We proposed that miR-196a can be used as a prognostic marker and a potential therapeutic target. View Full-Text
Keywords: liver cancer; microRNA; recurrence; stemness liver cancer; microRNA; recurrence; stemness
Show Figures

Figure 1

MDPI and ACS Style

Wang, S.-Y.; Chen, C.-L.; Hu, Y.-C.; Chi, Y.; Huang, Y.-H.; Su, C.-W.; Jeng, W.-J.; Liang, Y.-J.; Wu, J.-C. High Expression of MicroRNA-196a is Associated with Progression of Hepatocellular Carcinoma in Younger Patients. Cancers 2019, 11, 1549. https://doi.org/10.3390/cancers11101549

AMA Style

Wang S-Y, Chen C-L, Hu Y-C, Chi Y, Huang Y-H, Su C-W, Jeng W-J, Liang Y-J, Wu J-C. High Expression of MicroRNA-196a is Associated with Progression of Hepatocellular Carcinoma in Younger Patients. Cancers. 2019; 11(10):1549. https://doi.org/10.3390/cancers11101549

Chicago/Turabian Style

Wang, Shen-Yung, Chih-Li Chen, Yu-Chen Hu, Yi Chi, Yen-Hua Huang, Chien-Wei Su, Wen-Juei Jeng, Yuh-Jin Liang, and Jaw-Ching Wu. 2019. "High Expression of MicroRNA-196a is Associated with Progression of Hepatocellular Carcinoma in Younger Patients" Cancers 11, no. 10: 1549. https://doi.org/10.3390/cancers11101549

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop