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Knockdown of Circ_0003506 Impedes Radioresistance, Cell Growth, Migration and Invasion in Gastric Cancer

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Abstract

Background

Radioresistance is a major obstacle for clinical treatment of gastric cancer (GC). has_circ_0003506 (circ_0003506) was reported as an oncogenic factor in GC, but its effect on radioresistant GC is unclear.

Aims

This study aimed to explore the role of circ_0003506 in radioresistance and regulatory mechanism.

Methods

The expression detection was performed by real-time polymerase chain reaction. Cell survival was analyzed by colony formation assay. Cell proliferation was measured by Cell Counting Kit-8 assay and colony formation assay. Cell migration and invasion were examined using transwell assay. Cell apoptosis was assessed by flow cytometry. The target binding was confirmed via dual-luciferase reporter assay. The protein level was determined through western blot. Animal assay was performed for the functional exploration of circ_0003506 on radiosensitivity in vivo.

Results

Circ_0003506 was upregulated in radioresistant GC cells. Downregulation of circ_0003506 inhibited radioresistance to repress proliferation, migration and invasion but increase apoptosis in radioresistant GC cells. Circ_0003506 was a sponge of miR-1256. The effects of si-circ_0003506 on radioresistant GC cells were reverted by miR-1256 inhibitor. MiR-1256 suppressed tumor progression in radioresistant GC cells by downregulating bone morphogenetic protein type 2 receptor. Circ_0003506 regulated the level of bone morphogenetic protein type 2 receptor by targeting miR-1256. Downregulating circ_0003506 increased radiosensitivity of GC in vivo via regulating miR-1256 and bone morphogenetic protein type 2 receptor.

Conclusion

Knockdown of circ_0003506 suppressed radioresistance in GC through the regulation of miR-1256/bone morphogenetic protein type 2 receptor axis. Circ_0003506 might be a therapeutic target in radiotherapy of GC.

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The First People’s Hospital of Chenzhou, Chenzhou, China

    Kaikai Zhou, Jianwen Zhang & Shunxin Song

  2. Department of Oncology, Affiliated Hospital of Xiangnan University, No.25, Renmin West Road, Chenzhou, 423000, Hunan, People’s Republic of China

    Kaihong Xie & Xiaonan Hu

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  1. Kaikai Zhou
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  2. Jianwen Zhang
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  3. Shunxin Song
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  4. Kaihong Xie
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Correspondence to Xiaonan Hu.

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Zhou, K., Zhang, J., Song, S. et al. Knockdown of Circ_0003506 Impedes Radioresistance, Cell Growth, Migration and Invasion in Gastric Cancer. Dig Dis Sci 68, 128–137 (2023). https://doi.org/10.1007/s10620-022-07534-4

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  • DOI: https://doi.org/10.1007/s10620-022-07534-4

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