Abstract
Background/Aim Curcumin exhibits anticancer effects against various types of cancer including hepatocellular carcinoma (HCC). miR-21 has been reported to be involved in the malignant biological properties of HCC. However, whether miR-21 plays a role in curcumin-mediated treatment of HCC is unknown. The purpose of this study was to identify the potential functions and mechanisms of miR-21 in curcumin-mediated treatment of HCC. Methods The anticancer effects of curcumin were assessed in vivo and in vitro. The underlying mechanism of miR-21 in curcumin-mediated treatment of HCC was assessed by quantitative real-time PCR (RT-qPCR), western blot, and Dual-Luciferase Reporter assays. Results The present study revealed that curcumin suppressed HCC growth in vivo and inhibited HCC cell proliferation and induced cell apoptosis in a dose-dependent manner in vitro. Meanwhile, the curcumin treatment can downregulate miR-21 expression, upregulate TIMP3 expression, and inhibit the TGF-β1/smad3 signaling pathway. miR-21 inhibition enhanced the effect of curcumin on cell proliferation inhibition, apoptosis, and TGF-β1/smad3 signaling pathway inhibition in HepG2 and HCCLM3 cells. It demonstrated that TIMP3 was a direct target gene of miR-21. Interestingly, the effect of miR-21 inhibition on cell proliferation, apoptosis, and TGF-β1/smad3 signaling pathway in HepG2 and HCCLM3 cells exposed to curcumin was attenuated by TIMP3 silencing. Conclusion Taken together, the present study suggests that miR-21 is involved in the anticancer activities of curcumin through targeting TIMP3, and the mechanism possibly refers to the inhibition of TGF-β1/smad3 signaling pathway.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, ranking the fifth most prevalent cancer worldwide and the third most common cause of cancerrelated death [1]
The present study suggests that miR-21 is involved in the anticancer activities of curcumin through targeting TIMP3, and the mechanism possibly refers to the inhibition of TGF-β1/smad3 signaling pathway
Considering the fact that miRNAs play an important role in HCC, we first discussed the expression of miR-21 following curcumin treatment in vivo. e RT-qPCR results revealed that miR-21 expression was significantly downregulated (Figure 1(c)), indicating that miR-21 was important for the Relative mRNA levels
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, ranking the fifth most prevalent cancer worldwide and the third most common cause of cancerrelated death [1]. Several clinical protocols, including conventional chemotherapy, liver transplantation, surgical resection, and radiofrequency ablation, have been used to treat HCC [2]. These treatments are often ineffective due to late diagnosis, frequent recurrence, and low objective response rate [3], resulting in the 5-year overall survival rate of HCC patients remaining less than 18% [4]. Curcumin has been reported to inhibit the proliferation of various types of cancer, including HCC. Curcumin exerts powerful anticancer properties mainly by regulating a series of signaling pathways and molecular targets, such as PI3K/
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