microRNA-1266-5p directly targets DAB2IP to enhance oncogenicity and metastasis in oral cancer

Chih-Yu Peng; Che-Yi Lin; Szu-Han Chen; Yi-Wen Liao; Cheng-Chia Yu; Shiao-Pieng Lee

doi:10.1016/j.jds.2021.11.001

microRNA-1266-5p directly targets DAB2IP to enhance oncogenicity and metastasis in oral cancer

J Dent Sci. 2022 Apr;17(2):718-724. doi: 10.1016/j.jds.2021.11.001. Epub 2021 Nov 26.

Authors

Chih-Yu Peng^{1

2}, Che-Yi Lin^{3

4

5}, Szu-Han Chen¹, Yi-Wen Liao^{6

7}, Cheng-Chia Yu^{1

2

7}, Shiao-Pieng Lee^{4

5

8}

Affiliations

¹ School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
² Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
³ Division of Oral and Maxillofacial Surgery, Department of Dentistry, Chi Mei Medical Center, Tainan, Taiwan.
⁴ Division of Oral and Maxillofacial Surgery, Department of Dentistry, Tri-Service General Hospital, Taipei, Taiwan.
⁵ School of Dentistry, National Defense Medical Center, Taipei, Taiwan.
⁶ Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁷ Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
⁸ Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan.

Abstract

Background/purpose: Oral cancer has been recognized as one of the most common malignancies worldwide and ranks the fifth leading cause of cancer death in Taiwan. A variety of studies have demonstrated that microRNAs are involved in the regulation of the hallmarks of oral carcinogenesis. Nevertheless, the effect of miR-1266-5p on the tumorigenesis of oral cancer has not been investigated, and not to mention, its functional role in oral cancer.

Materials and methods: The upregulation of miR-1266-5p in SASVO3 and SASM5 cells was identified by RNA-Seq and examined by qRT-PCR analysis. The phenotypic assays including proliferation activity, migration capacity, invasion, wound healing, and colony-forming abilities were conducted in oral cancer cells after knockdown of miR-1266-5p. Luciferase reporter and western blotting were used to validate DAB2IP was a direct target of miR-1266-5p in oral cancer.

Results: We identified that miR-1266-5p was significantly overexpressed in highly tumorigenic SASVO3 cells and metastatic SASM5 cells. qRT-PCR revealed that miR-1266 significantly increased upregulated in oral cancer and lymph node metastatic tissues compared to normal counterparts We found that downregulation of miR-1266-5p inhibited the proliferation and clonogenicity capacities of SASVO3 cells. Knockdown of miR-1266-5p also inhibited migration/invasion and self-renewal abilities in SASM5 cells. Moreover, we validated miR-1266-5p directly bound to the 3'UTR of DAB2IP in oral cancer cells. We found that DAB2IP knockdown reversed the inhibitory effects of self-renewal and migration mediated by silencing of miR-1266-5p.

Conclusion: miR-1266 functions as a biomarker in oral cancer patients, and downregulation of miR-1266 may ameliorate the oncogenic and metastasis potential of oral cancer by targeting DAB2IP.

Keywords: DAB2IP; Metastasis; MicroRNA-1266-5p; Oral cancer.