Geqiong Xiao1, Hui Liao1, Mengyu Ding1, Qiong Wang1, Wenwen Zhu1, Jian Chang1, Liang Wang2
1Department of Oncology, Affiliated Hospital of Shaoxing University, Shaoxing, China
2Department of Radiology, Affiliated Hospital of Shaoxing University, Shaoxing, China
Summary
Purpose: Liver hepatocellular carcinoma (LIHC) is characterized by high recurrence and poor prognosis. This study aimed to explore how miR-378a-3p affects the progression of LIHC.
Methods: The expression of miR-378a-3p in LIHC and normal tissues, as well as in LIHC cell lines HepG2, 97H, SNU423, SNU449, and SMMC-7721, was detected. Then, miR-378a-3p was overexpressed to evaluate its function on LIHC cell proliferation, migration, and invasion. Bioinformatics analysis was used to predict the target of miR-378a-3p. Subsequently, the effects of SIRT6 on LIHC cell proliferation, migration, and invasion, and the interaction between miR-378a-3p and SIRT6 were investigated. Xenograft models were established to conduct the functional experiment in vivo.
Results: miR-378a-3p was lowly expressed in LIHC. Moreover, miR-378a-3p overexpression could repress LIHC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), and meanwhile facilitates its apoptosis. Mechanistically, we determined that miR-378a-3p could directly bind to the 3’-UTR of Human sirtuin 6 (SIRT6). Based on rescue experiment, we found that miR-378a-3p overexpression restrained LIHC cells malignant behaviors, including proliferation, invasion, and EMT process, while which could be remedied by SIRT6 overexpression. More importantly, through injecting miR-378a-3p-agomir into nude mice, we noticed that miR-378a-3p overexpression efficiently suppressed the weight and volume of xenograft tumor, and meanwhile prevented the Ki67 expression and EMT process in tumor formed by miR-378a-3p-overexpressed 97H cells.
Conclusions: miR-378a-3p/SIRT6 axis could serve as a potential candidate for the treatment of LIHC.
Keywords: liver hepatocellular carcinoma, miR-378a-3p, SIRT6, tumor, apoptosis, migration, invasion, EMT.
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