The present study found a significant negative correlation b
The present study found a significant negative correlation between miR-152-3p and CDK8 expression in human HCC tissues. We also validated that CDK8 was a direct target of miR-152-3p, and overexpression of miR-152-3p inhibited proliferation and induced apoptosis in HCC Tariquidar mg by suppressing CDK8 expression.
Material and methods
Discussion CDK8 is a functional transcription factor in various cancers and may be a potential anticancer target . In fact, CDK8 seems not to be a necessary factor for transcription, knockdown of CDK8 has not achieved histopathological abnormalities in the young adult mouse . In contrast to that, CDK8 deficiency results in the developmental arrest of embryogenesis in mice . These findings imply that CDK8 plays multiple roles during different physiological and pathological phases. Recently, CDK8 as an oncogene promotes the growth and metastasis of colon cancer . In addition, CDK8 is amplified in several cancer types, including colorectal cancer , breast cancer  and laryngeal squamous cell carcinoma . Intriguingly, Zhang et al reveals that up-regulation of CDK8 is observed in HCC tissues and associated with lung metastasis . However, the association between CDK8 and survival prognosis in HCC patients has not been clarified in this paper . In our study, we also found that CDK8 expression levels were significantly elevated in HCC tissues, and higher CDK8 expression level was dramatically correlated with poorer OS and DFS in HCC patients. These findings showed CDK8 as an independent factor for predicting the survival prognosis of HCC patients. On the other hand, CDK8 as a direct target of miR-152-3p could be post-transcriptionally repressed by miR-152-3p. The expression of CDK8 was significantly inversely correlated with miR-152-3p expression in HCC tissues. Overexpression of miR-152-3p had the ability to inhibit proliferation and induce apoptosis in HCC cells by inhibiting CDK8 signaling. Similarly, miR-26a inhibits the progression and metastasis of HCC by CDK8-modulated c-Myc/EZH2 signaling . However, the downstream signaling pathways of CDK8 had not been dabbled in our study. These may be the limitations in the present study. Previous studies substantiate that inhibition of CDK8 can impede tumor growth in several types of cancers, which have expedited the development of CDK8 inhibitors as potential anticancer agents . Confusedly, some researchers have suggested that CDK8 knockout is distinct from pharmacological inhibition of CDK8. For example, CDK8 inhibitor has not enough activity to resist proliferation in HCT116 cells, while CDK8 knockout exerts the anti-proliferative activity in these cells . As an endogenous inhibitor of CDK8, miR-152-3p has been reported as an onco-suppressor in prostate cancer , glioma  and breast cancer . In our study, we also found that miR-152-3p had an antineoplastic activity in vitro, reflecting that overexpression of miR-152-3p restrained cell proliferation and increased the apoptotic cell proportion in HepG2 and SMMC7721 cells. However, the anti-proliferative and pro-apoptotic roles of miR-152-3p were restricted by CDK8 after co-transfection with the miR-152-3p mimics and the CDK8 overexpressed plasmids. These findings suggested that CDK8 and miR-152-3p might play the reciprocal roles in the progression of HCC. Additionally, high miR-152-3p expression was associated with longer OS and DFS in HCC patients. The correlation analysis had documented a significant negative correlation between miR-152-3p and CDK8 in the HCC tissues. The present results obtained forcefully proved that miR-152-3p exhibited a similar function of CDK8 inhibitor and might be vital for the therapeutic application in the treatment of HCC. The correlation between miR-152-3p and CDK8 mRNA expression levels in HCC tissues was significantly negatively correlated (Fig. 3B). in vitro experiments, we found that only the protein expression of CDK8 was decreased in HepG2 and SMMC7721 cells after transfection with miR-152-3p mimics (Fig. 4C). Therefore, there is no direct evidence that miR-152-3p shows the ability to degrade CDK8 mRNA. One possible reason is that accumulation of multiple gene mutations and their interactions contribute to the initiation and progression of HCC. The present study revealed that miR-152-3p as a translational repressor decreased the protein expression of CDK8, and miR-152-3p/CDK8 signaling pathway, at least partially, participated in hepatic tumorigenesis.