Abstract
Researches have pointed that piplartine inhibits the proliferation of hepatocellular carcinoma (HCC) cells, however, the underlying mechanisms has not been well defined. Currently, more and more studies have pointed out that circRNAs can regulate tumor cell proliferation, involve in the tumorigenesis mechanism of various tumors. In this study, we explored whether piplartine may participate in the development of HCC through the regulation of ability of HCC cell proliferation by circRNA. Based on the chip analysis, we selected candidate circRNAs that are highly correlated with HCC. CircRNA expression in OSCC cells treated with piplartine was detected by qRT‐PCR. We found that only the expression of hsa_circ_100338 (circ‐100338) was observably reduced. The expression characteristics of circ‐100338 in HCC cell lines were also verified by qRT‐PCR. Subsequently, whether or notcirc‐100338 can regulate ZEB1 via competitively binding to miR‐141‐3p was determined by the RIP assay and dual luciferase reporter gene assay. The effect of the circ‐100338/miR‐141‐3p/ZEB1 axis on the proliferation of HCC cell was tested by EdU and CCK‐8 assay. Results showed that circ‐100338 expression was observably increased in HCC cell lines. Simultaneously, circ‐100338 can regulate the expression of ZEB1by competitively binding to miR‐141‐3p. Moreover high expression of circ‐100338 can stimulate the proliferation of HCC cells. Our current study revealed that circ‐100338 played as a ceRNA in promoting the progression of HCC by sponging miR‐141‐3p, while piplartine can participate in the development of HCC by inhibiting the expression of circ‐100338.
Highlights
Hepatocellular carcinoma (HCC) is the commonest liver cancer[1] and is one of leading cause of cancer-related mortality
The results demonstrated that the level of circ-100338 and circRNA-102533 in HCC cell lines was significantly increased compared toHL-7702(Figure 1A), which is consistent with the chip prediction
The results demonstrated that only the expression of circ-100338 was lowered obviously after treatment of HCC cell lines with piplartine (Figure 1B)
Summary
Hepatocellular carcinoma (HCC) is the commonest liver cancer[1] and is one of leading cause of cancer-related mortality. Zhang et al confirmed reducing of exosome transmitted miR-320a from cancer-associated fibroblasts promotes HCC metastasis and proliferation.[7]. These findings have not yet fully revealed the pathogenesis of HCC, thereby it has important clinical value to further research the occurrence and development of HCC from the epigenetic perspective. Previous studies have confirmed that piplartine has a therapeutic effect on hepatocellular carcinoma.[21]. Whether it can affect the regulation of expression of circRNA to participate in tumorigenesis mechanism requires further exploration, so we have made a further study from the perspective of epigenetics. We confirmed that the piplartine suppresses proliferation of hepatocellular carcinoma by circ-100338 function as competitive endogenous RNA by a sequence of assays
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