J Cancer 2022; 13(1):34-50. doi:10.7150/jca.62927 This issue

Research Paper

Hsa_circ_0074298 promotes pancreatic cancer progression and resistance to gemcitabine by sponging miR-519 to target SMOC

Chen Hong1, Wang Lishan2, Xie Peng1, Lei Zhengqing2, Yang Yang2, Hu Fangfang2, Yu Zeqian2, Cheng Zhangjun2, Zhou Jiahua2✉

1. Department of Hepatopancreatobiliary Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, 210009, China.
2. Department of Hepatopancreatobiliary Surgery, Zhongda Hospital Southeast University, Nanjing, Jiangsu Province, 210009, China.

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Citation:
Hong C, Lishan W, Peng X, Zhengqing L, Yang Y, Fangfang H, Zeqian Y, Zhangjun C, Jiahua Z. Hsa_circ_0074298 promotes pancreatic cancer progression and resistance to gemcitabine by sponging miR-519 to target SMOC. J Cancer 2022; 13(1):34-50. doi:10.7150/jca.62927. Available from https://www.jcancer.org/v13p0034.htm

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Abstract

Graphic abstract

Objective: To investigate the expression of hsa_circ_0074298 (circular RNA) and the molecular mechanism that promotes tumor growth and enhances the chemoresistance of pancreatic cancer.

Methods: Real-time reverse transcription-PCR was used to detect hsa_circ_0074298 expression in pancreatic cancer. The intracellular localization of hsa_circ_0074298 was determined by RNA in situ hybridization. The CCK8 method, colony formation assay, Transwell assay, and flow cytometry were used to evaluate the effects of hsa_circ_0074298 on the proliferation, migration, invasion, cell cycle, apoptosis of pancreatic cancer cells. Bioinformatics analysis and dual luciferase assays were employed to detect the association of hsa_circ_0074298 and miR-519d and the binding of miR-519d to the target gene SMOC2. A subcutaneous xenograft model was established to observe the effect of hsa_circ_0074298 in vivo.

Results: The hsa_circ_0074298 was mainly localized in the cytoplasm. Hsa_circ_0074298 was highly expressed in pancreatic cancer tissues and cell lines. The expression of hsa_circ_0074298 was significantly correlated with pancreatic cancer tumor size, lymph node metastasis, and pathological grade. hsa_circ_0074298 could sponge miR-519, and miR-519d bound to SMOC2. Downregulation of hsa_circ_0074298 expression significantly inhibited cell proliferation, migration, invasion, colony forming ability and promoted cell cycle arrest, apoptosis and chemo-resistance of pancreatic cancer in vitro and vivo. However, the effects could be reversed by a miR-519d inhibitor or SMOC2 overexpression.

Conclusion: By sponging miR-519 and targeting SMOC2, hsa_circ_0074298 promotes the growth and metastasis of pancreatic cancer and increases the resistance of pancreatic cancer cells to gemcitabine.

Keywords: hsa_circ_0074298, miR-519d, SMOC2 gene, pancreatic cancer, chemo-resistance