In:
British Journal of Cancer, Springer Science and Business Media LLC, Vol. 128, No. 2 ( 2023-01-19), p. 363-374
Abstract:
Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum -induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum -induced chemoresistance and explore the mechanism. Methods The role of metformin in F. nucleatum -infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum -mediated regulation of the sonic hedgehog pathway. Results We found that metformin abrogated F. nucleatum -promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum -stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum -induced stemness, thereby rescuing F. nucleatum -triggered chemoresistance in CRC. Conclusions Metformin acts on F. nucleatum -infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum -triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum .
Type of Medium:
Online Resource
ISSN:
0007-0920
,
1532-1827
DOI:
10.1038/s41416-022-02044-6
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2002452-6
detail.hit.zdb_id:
80075-2
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