Co-upregulation of miR-31 and its host gene lncRNA MIR31HG in oral squamous cell carcinoma

Hsi-Feng Tu; Chung-Ji Liu; Wan-Wen Hung; Tzong-Ming Shieh

doi:10.1016/j.jds.2021.11.006

Co-upregulation of miR-31 and its host gene lncRNA MIR31HG in oral squamous cell carcinoma

J Dent Sci. 2022 Apr;17(2):696-706. doi: 10.1016/j.jds.2021.11.006. Epub 2021 Nov 27.

Authors

Hsi-Feng Tu^{1

2

3}, Chung-Ji Liu^{1

4}, Wan-Wen Hung², Tzong-Ming Shieh⁵

Affiliations

¹ Department of Dentistry, College of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Institute of Oral Biology, College of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Department of Stomatology, National Yang Ming Chiao Tung University Hospital, Yi-Lan, Taiwan.
⁴ Department of Dentistry, Taipei MacKay Memorial Hospital, Taipei, Taiwan.
⁵ Department of Dentistry, College of Dentistry, China Medical University, Taichung, Taiwan.

Abstract

Background/purpose: Several long non-coding RNAs (lncRNAs) harbor miRNA in their genome. MIR31HG harbors miR-31 in its intron and it is speculated that they are co-expressed in tumors. This study addressed whether frequent miR-31 and MIR31HG co-upregulation occurred in oral squamous cell carcinoma (OSCC) and its clinical implications.

Materials and methods: Microarray was performed to retrieve dis-regulated lncRNAs from tissue sample. The ectopic gene expression was carried out to specify the phenotypic influences of selected lncRNA screened from bioinformatic algorithms. The expression of miR-31 and MIR31HG in tissues or scrapped samples was analyzed using qRT-PCR. The implications of gene expression as related to metastasis or survival were further dissected.

Results: Microarray identified disrupted transcripts including MIR31HG and other 152 lncRNAs aberrantly expressed in OSCC tissues. In silico algorithms annotated an eminent involvement of aberrant transcripts in the regulation of cell cycle, extracellular modulation, adhesion, and wound healing. The enhancement of proliferation, wound healing, invasion and anchorage-independent colony formation mediated by MIR31HG was ascertained by ectopic expression in OECM1 cells. Besides, co-upregulation of miR-31 and MIR31HG was conspicuous in OSCC tissues. High expression of miR-31 and MIR31HG designated a trend of worse OSCC prognosis. Interestingly, high MIR31HG expression defined a very poor survival in stage IV diseases. By contrast, high miR-31 expression predicted nodal metastasis in stage I-III diseases.

Conclusion: Assessment of miR-31 and MIR31HG expression in OSCC may enable the prognostic prediction. The candidate lncRNAs isolated from this work can be further validated as crucial factors contributing to OSCC pathogenesis.

Keywords: Carcinoma; MIR31HG; Mouth; Oral; miR-31.