KRAS mutations upregulate Runx1 to promote occurrence of head and neck squamous cell carcinoma

Miao Deng; Jiaxin Guo; Zihang Ling; Chi Zhang; Lihong He; Zhaona Fan; Bin Cheng; Juan Xia

doi:10.1002/mc.23563

KRAS mutations upregulate Runx1 to promote occurrence of head and neck squamous cell carcinoma

Mol Carcinog. 2023 Sep;62(9):1284-1294. doi: 10.1002/mc.23563. Epub 2023 May 24.

Authors

Miao Deng^{1

2

3}, Jiaxin Guo^{1

2

3}, Zihang Ling^{1

2

3}, Chi Zhang^{1

2

3}, Lihong He^{1

2

3}, Zhaona Fan^{1

2

3}, Bin Cheng^{1

2

3}, Juan Xia^{1

2

3}

Affiliations

¹ Hospital of Stomatology, Sun Yat-sen University, Guangzhou, P. R. China.
² Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, P. R. China.
³ Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, P. R. China.

PMID: 37222390
DOI: 10.1002/mc.23563

Abstract

Gene mutations play an important role in head and neck squamous cell carcinoma (HNSCC) by not only promoting the occurrence and progression of HNSCC but also affecting sensitivity to treatment and prognosis. KRAS is one of the most frequently mutated oncogenes, which has been reported to have a mutation rate from 1.7% to 12.7% and may lead to poor prognosis in HNSCC, but its role remains unclear. Here, we found that the KRAS mutation can promote HNSCC generation through synergism with 4-Nitroquinoline-1-Oxide(4NQO). Mechanistically, KRAS mutations can significantly upregulate Runx1 to promote oral epithelial cell proliferation and migration and inhibit apoptosis. Runx1 inhibitor Ro 5-3335 can effectively inhibit KRAS-mutated HNSCC progression both in vitro and in vivo. These findings suggest that the KRAS mutation plays an important role in HNSCC and that Runx1 may be a novel therapeutic target for KRAS-mutated HNSCC.

Keywords: HNSCC; KRAS; Ro 5-3335; Runx1; animal model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell* / pathology
Cell Line, Tumor
Head and Neck Neoplasms* / genetics
Humans
Mutation
Proto-Oncogene Proteins p21(ras) / genetics
Squamous Cell Carcinoma of Head and Neck / genetics

Substances

Proto-Oncogene Proteins p21(ras)
KRAS protein, human