Abstract
Chemotherapeutic insensitivity is a major obstacle for effective treatment of hepatocellular carcinoma (HCC). Recently, new evidence showed that microRNAs (miRNAs) are closely related to drug sensitivity. This study aimed to investigate the relationship between miR-138 expression and cisplatin sensitivity of HCC cells by regulation of EZH2. CCK-8, EdU, and western blotting are determining the cell viability, proliferation, EZH2, and EMT-related protein expression. It was found that compared with normal samples, miR-138 expression was lower in cancer tissue; it was also downregulated in HCC cells. Transfected with miR-138 mimic increased sensitivity of HCC cells to cisplatin. Mechanistically, Luciferase Reporter analysis verified the interaction between miR-138 and target gene EZH2. Inhibition of EZH2 enhanced cisplatin sensitivity and transfection with EZH2 mimic mirrored the function of miR-138 in cisplatin sensitivity. Furthermore, the role of miR-138 on reversed cisplatin-induced epithelial–mesenchymal transition (EMT) was attenuated when combined with EZH2 plasmid. In conclusion, all data from this study illustrate that miR-138 may as a tumor suppressor provides a potential treatment method to treating HCC.
Highlights
Hepatocellular carcinoma (HCC) is a very aggressive malignancy tumor all over the world, which is characterized by easy recurrence and metastasis, poor prognosis, and high mortality [1]
To explore the potential effect of miR-138 in HCC, starBase v.3 was performed to analyze the level of miR-138 in liver hepatocellular carcinoma (LIHC), showing that it was reduced in 370 LIHC samples compared with 50 normal samples (Figure 1(a))
RT-qPCR that compared with the normal liver cells, miR-138 expression was decreased in HCC cells (Figure 1(b))
Summary
Hepatocellular carcinoma (HCC) is a very aggressive malignancy tumor all over the world, which is characterized by easy recurrence and metastasis, poor prognosis, and high mortality [1]. Used therapeutic regimens include 5-fluorouracil (5-FU), sorafenib, adriamycin, camptothecin, and gemcitabine [2, 3]. Cisplatin is a widely used first-line chemotherapeutic drug for the treatment in a variety of cancers, such as HCC [4, 5]. The clinical applications of cisplatin have been largely restricted [6]. Chemotherapy resistance limits the use of therapy for HCC. Solving the mechanisms of chemotherapy resistance in HCC is an important issue that we need to pay more attention
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