机构:[1]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111, Xianxia Road, Shanghai 200336, China[2]The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China[3]The Department of Reproductive Genetic Center, Changhai Hospital, Second Military Medical University, Shanghai 200433, China[4]Department of Laboratory, Shunyi District Hospital, Beijing 101300, China
Circular RNAs (circRNAs) play important roles in the progression of hepatocellular carcinoma (HCC). However, the exact function of circ_0008934 in HCC is unknown. Our study aimed to investigate the expression characteristics of circ_0008934 in HCC and its effects on the proliferation and metastasis of HCC, and to explore the potential mechanism. In this study, circ_0008934 expression was found to be significantly upregulated in HCC tissues and cell lines by qRT-PCR. High level of circ_0008934 is closely associated with higher serum AFP (P < 0.001), larger tumor diameter (P = 0.012), microvascular invasion (P = 0.008) and poorer prognosis (P = 0.007) of HCC patients. Functionally, knockdown of circ_0008934 inhibited HCC cell proliferation, invasion and migration in vitro and vivo. Mechanically, circ_0008934 was a sponge of miR-1305 to facilitate the TMTC3 expression, and the TMTC3 expression in HCC tissues was negatively associated with the survival of HCC patients. Furthermore, rescued assays revealed that the circ_0008934 facilitated HCC proliferation, invasion and migration by regulating miR-1305/ TMTC3 signaling pathways. Overall, these results demonstrate that downregulation of circ_0008934 repress HCC growth and metastasis by upregulating miR-1305 to inhibit TMTC3, suggesting circ_0008934/ miR-1305/ TMTC3 regulatory axis may be a possible novel therapeutic target for HCC.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672335]; Project of Shanghai Municipal Commission of Health and Family Planning [201740055]; Medical engineering cross project of Shanghai Jiao Tong University [YG2022QN115, ZH2018QNB26]; Shanghai Tongren Hospital [2019shtrxx09]; Scientific Research Project of Changning District Health [20194Y001]