HBV Promotes the Proliferation of Liver Cancer Cells through the hsa_circ_0000847/miR-135a Pathway

Jianjun Lin; Xiang Lian; Shihang Xue; Lian Ouyang; Lihui Zhou; Yuyang Lu; Longteng Xie

doi:10.1155/2022/7332337

HBV Promotes the Proliferation of Liver Cancer Cells through the hsa_circ_0000847/miR-135a Pathway

Evid Based Complement Alternat Med. 2022 Sep 15:2022:7332337. doi: 10.1155/2022/7332337. eCollection 2022.

Authors

Jianjun Lin¹, Xiang Lian², Shihang Xue³, Lian Ouyang⁴, Lihui Zhou⁴, Yuyang Lu⁵, Longteng Xie²

Affiliations

¹ Department of Clinical Laboratory, Xiangshan First People's Hospital, Ningbo Fourth Hospital, Ningbo 315700, China.
² Hepatology Department, Xiangshan First People's Hospital, Ningbo Fourth Hospital, Ningbo 315700, China.
³ Department of General Surgery, Xiangshan First People's Hospital, Ningbo Fourth Hospital, Ningbo 315700, China.
⁴ Department of Orthopaedic Surgery, Xiangshan First People's Hospital, Ningbo Fourth Hospital, Ningbo 315700, China.
⁵ Xiangshan County Center for Disease Control and Prevention, Ningbo 315700, China.

Abstract

Hepatocellular carcinoma (HCC) is currently one of the most common tumors, with a high morbidity and mortality rate. HCC induced by persistent hepatitis B virus (HBV) infection is the most common liver cancer subtype at present, and HBV-related HCC is highly malignant and its development mechanism still needs to be explored in depth. This study aimed to explore the molecular mechanism of hsa_circ_0000847 targeting miR-135a-5p (miR-135a) to regulate the proliferation, invasion, and apoptosis of liver cancer cells. The study found that the expression level of hsa_circ_0000847 in liver cancer tissues and cells was significantly increased, while the expression level of miR-135a was significantly decreased. Hsa_circ_0000847 promoted the proliferation of liver cancer cells and elevated the expression of the proliferation-related protein. In addition, hsa_circ_0000847 could promote the invasion of HBV-infected liver cancer cells and inhibit the cell apoptosis of liver cancer cells. At the same time, it significantly promoted the expression of antiapoptotic proteins and inhibited the expression of proapoptotic protein. Interestingly, the dual luciferase experiment proved that hsa_circ_0000847 directly targeted miR-135a. On the other hand, the combined effect of hsa_circ_0000847 and miR-135a further illustrated the effect of hsa_circ_0000847 on the proliferation, invasion, and apoptosis of liver cancer cells. In addition, further experiments have also found that HBV could promote the expression of p-p38, p-ERK, and p-JNK through the hsa_circ_0000847/miR-135a axis, thereby further activating the MAPK pathway. In short, HBV promotes the proliferation and invasion of liver cancer cells and inhibits apoptosis by regulating the hsa_circ_0000847/miR-135a pathway, which provided a theoretical basis for effective treatment of HBV-infected liver cancers.