Activation of DDX58/RIG‑I suppresses the growth of tumor cells by inhibiting STAT3/CSE signaling in colon cancer

Deng,Yuying; Fu,Han; Han,Xue; Li,Yuxi; Zhao,Wei; Zhao,Xuening; Yu,Chunxue; Guo,Wenqing; Lei,Kaijian; Wang,Tianxiao

doi:10.3892/ijo.2022.5410

Activation of DDX58/RIG‑I suppresses the growth of tumor cells by inhibiting STAT3/CSE signaling in colon cancer

Authors:
- Yuying Deng
- Han Fu
- Xue Han
- Yuxi Li
- Wei Zhao
- Xuening Zhao
- Chunxue Yu
- Wenqing Guo
- Kaijian Lei
- Tianxiao Wang
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Affiliations: Biopharmaceutical Department, School of Pharmacy, Henan University, Kaifeng, Henan 475004, P.R. China
Published online on: August 19, 2022 https://doi.org/10.3892/ijo.2022.5410
Article Number: 120
Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Some patients with colon cancer eventually develop metastasis during treatment, and the 5‑year survival rate of patients with metastatic colon cancer remains relatively low, which is most likely due to the ineffectiveness of the current standard treatment. Systemic treatment for patients with colon cancer has expanded from chemotherapy to targeted therapy and immunotherapy. Immunotherapy holds promise in the treatment of colon cancer. The present study revealed the role of innate immune receptor helicase DExD/H‑box helicase 58 (DDX58), which encodes retinoic acid‑inducible gene‑I (RIG‑I), in colon cancer. It was demonstrated that colon cancer patients with a low protein expression of DDX58/RIG‑I had a worse 5‑year survival rate of patients compared with patients with a high expression of DDX58/RIG‑I. The activation of DDX58/RIG‑I inhibited the proliferation, migration and invasion of colon cancer cells, as well as tumor growth in a nude mouse xenograft model of colon cancer. To investigate the mechanisms of action of DDX58/RIG‑I in colon cancer, the role of signal transducer and activator of transcription 3 (STAT3)/cystathionine‑γ‑lyase (CSE) signaling in the up‑ or downregulation of DDX58 was examined. The data demonstrated that DDX58 regulated the STAT3/CSE signaling pathway by interacting with STAT3 and consequently affecting the proliferation of tumor cells in colon cancer. In addition, the RIG‑I agonist, SB9200, induced proliferation, migration and invasion of human colon cancer. On the whole, the present study demonstrates that DDX58/RIG‑I affects the proliferation of tumor cells by regulating STAT3/CSE signaling in colon cancer. The findings presented herein suggest that DDX58/RIG‑I activation may be an effective treatment strategy, and DDX58/RIG‑I agonists may be potential therapeutic candidates for colon cancer.

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