A novel melatonin-regulated lncRNA suppresses TPA-induced oral cancer cell motility through replenishing PRUNE2 expression

Shih-Chi Su^{1

2

3}, Chia-Ming Yeh^{4

5}, Chiao-Wen Lin^{6

7}, Yi-Hsien Hsieh^{4

5}, Chun-Yi Chuang^{8

9}, Chih-Hsin Tang^{10

11}, Yi-Chan Lee^{12

13}, Shun-Fa Yang^{4

5}

Affiliations

¹ Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
² Drug Hypersensitivity Clinical and Research Center, Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan.
³ Central Research Laboratory, XiaMen Chang Gung Hospital, XiaMen, China.
⁴ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁵ Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁶ Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
⁷ Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁸ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁹ Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan.
¹⁰ Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.
¹¹ Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
¹² Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan.
¹³ College of Medicine, Chang Gung University, Taoyuan, Taiwan.

PMID: 34339541
DOI: 10.1111/jpi.12760

A novel melatonin-regulated lncRNA suppresses TPA-induced oral cancer cell motility through replenishing PRUNE2 expression

Shih-Chi Su et al. J Pineal Res. 2021 Oct.

. 2021 Oct;71(3):e12760.

doi: 10.1111/jpi.12760. Epub 2021 Aug 26.

Authors

Shih-Chi Su^{1

2

3}, Chia-Ming Yeh^{4

5}, Chiao-Wen Lin^{6

7}, Yi-Hsien Hsieh^{4

5}, Chun-Yi Chuang^{8

9}, Chih-Hsin Tang^{10

11}, Yi-Chan Lee^{12

13}, Shun-Fa Yang^{4

5}

Affiliations

¹ Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
² Drug Hypersensitivity Clinical and Research Center, Department of Dermatology, Chang Gung Memorial Hospital, Keelung, Taiwan.
³ Central Research Laboratory, XiaMen Chang Gung Hospital, XiaMen, China.
⁴ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁵ Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁶ Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
⁷ Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁸ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁹ Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan.
¹⁰ Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.
¹¹ Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
¹² Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan.
¹³ College of Medicine, Chang Gung University, Taoyuan, Taiwan.

PMID: 34339541
DOI: 10.1111/jpi.12760

Abstract

The inhibitory effect of melatonin on cancer cell dissemination is well established, yet the functional involvement of lncRNAs in melatonin signaling remains poorly understood. In this study, we identified a melatonin-attenuated lncRNA acting as a potential melatonin-regulated oral cancer stimulator (MROS-1). Downregulation of MROS-1 by melatonin suppressed TPA-induced oral cancer migration through replenishing the protein expression of prune homolog 2 (PRUNE2), which functioned as a tumor suppressor in oral cancer. Melatonin-mediated MROS-1/PRUNE2 expression and cell motility in oral cancer were regulated largely through the activation of JAK-STAT pathway. In addition, MROS-1, preferentially localized in the nuclei, promoted oral cancer migration in an epigenetic mechanism in which it modulates PRUNE2 expression by interacting with a member of the DNA methylation machinery, DNA methyltransferase 3A (DNMT3A). Higher methylation levels of PRUNE2 promoter were associated with nodal metastases and inversely correlated with PRUNE2 expression in head and neck cancer. Collectively, these findings suggest that MROS-1, serving as a functional mediator of melatonin signaling, could predispose patients with oral cancer to metastasize and may be implicated as a potential target for antimetastatic therapies.

Keywords: lncRNA; melatonin; metastasis; oral cancer.

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References

REFERENCES

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A novel melatonin-regulated lncRNA suppresses TPA-induced oral cancer cell motility through replenishing PRUNE2 expression

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A novel melatonin-regulated lncRNA suppresses TPA-induced oral cancer cell motility through replenishing PRUNE2 expression

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