Overexpression of transient receptor potential melastatin 6 during human oral squamous cell carcinogenesis

Yen-Yun Wang; Wen-Chen Wang; Chiang-Wei Su; Ching-Wei Hsu; Shyng-Shiou Yuan; Yuk-Kwan Chen

doi:10.1016/j.jds.2022.11.002

Overexpression of transient receptor potential melastatin 6 during human oral squamous cell carcinogenesis

J Dent Sci. 2023 Jan;18(1):382-391. doi: 10.1016/j.jds.2022.11.002. Epub 2022 Nov 14.

Authors

Yen-Yun Wang^{1

2}, Wen-Chen Wang^{1

3

4}, Chiang-Wei Su⁵, Ching-Wei Hsu⁵, Shyng-Shiou Yuan^{2

6

7

8}, Yuk-Kwan Chen^{1

3

4}

Affiliations

¹ School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Division of Oral Pathology & Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁴ Oral & Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵ Division of Oral & Maxillofacial Surgery, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁶ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷ Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁸ Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

Background/purpose: Transient receptor potential melastatin (TRPM) channel is involved in cell proliferation and cell survival. Eight members (TRPM1-8) are within the TRPM subfamily. The current study is aimed to investigate TRPM6 expression in human oral carcinogenesis.

Materials and methods: Sixty-six oral squamous cell carcinomas (OSCCs), 47 oral potentially malignant disorders (OPMD) with moderate-severe epithelial dysplasia (ED), 28 OPMD with mild ED, and 33 normal oral mucosa (NOM) samples were subjected to immunohistochemical staining. Two human oral cancer cell lines (OCCLs), an oral premalignant cell line (DOK), and a normal oral keratinocyte culture (HOK) were used for Western blot analysis. OCCLs were evaluated for proliferation, migration, invasion assays, and intracellular calcium concentration.

Results: TRPM6 protein expression in OSCC was significantly increased as compared with normal samples. Protein expression of TRPM6 in OCCLs was significantly higher as compared with HOK. Significant decreases in degrees of proliferation, migration, invasion, and intracellular calcium concentration were noted in OCCLs with TRPM6 siRNA transfection as compared with those without transfection. Significantly increased TRPM6 protein level was noted in OPMD with moderate-severe ED as compared with those with mild ED.

Conclusion: Our results implicate that TRPM6 overexpression is potentially related to human oral carcinogenesis.

Keywords: Calcium channel; Oral potentially malignant disorders; Oral squamous cell carcinoma; TRPM6.