Long non-coding RNA HOTAIR/microRNA-761 sponge regulates PPME1 and further influences cell biological functions in thyroid carcinoma

Runsheng Guo; Yong Ning; Ye Ma; Qianhuang Lin; Na Shen; Peidong Shi

doi:10.1002/lio2.593

Long non-coding RNA HOTAIR/microRNA-761 sponge regulates PPME1 and further influences cell biological functions in thyroid carcinoma

Laryngoscope Investig Otolaryngol. 2021 May 26;6(3):438-445. doi: 10.1002/lio2.593. eCollection 2021 Jun.

Authors

Runsheng Guo¹, Yong Ning¹, Ye Ma¹, Qianhuang Lin¹, Na Shen², Peidong Shi¹

Affiliations

¹ Department of General Surgery Jiading District Central Hospital Affiliated to Shanghai University of Medicine & Health Sciences Shanghai China.
² Department of Otolaryngology, Zhongshan Hospital Fudan University Shanghai China.

Abstract

Background: Most well-differentiated thyroid carcinomas display good therapeutic outcomes, but there are still some patients who are not sensitive to the general treatments lose their treatment opportunities. Thus, it is important to understand the molecular mechanisms that cause thyroid carcinoma, so as to find effective diagnostic and therapeutic targets.

Aim of the study: To explore the role of homeobox transcript antisense RNA (HOTAIR) in thyroid carcinoma through protein phosphatase methylesterase 1 (PPME1) by sponging microRNA 761 (miR-761).

Methods: The regulation network amongst HOTAIR, miR-761 and PPME1 was predicted by online sources. RT-PCR was conducted to evaluate the expression of HOTAIR and miR-761 in tumor tissues. Clinical data was collected and analyzed by Chi-square test. Cell apoptosis and proliferation was evaluated using three types of cancer cells (HTh-7, CAL-62, BCPAP) after treated with si-HOTAIR and miR-761inhibitor. The binding site among HOTAIR, miR-761 and PPME1 was verified by dual luciferase reporter assay. PPME1 expression was measured after HOTAIR and miR-761 were suppressed by western blot. Survival time was measured in nude mice using log-rank test.

Results: HOTAIR was expressed to a significantly greater extent than miR-761 in thyroid tumor tissues (P < .001). miR-761 and PPME1 were negatively correlated (coef = -1.91, P < .001). HOTAIR competitively binds to miR-761 and miR-761 directly targets PPME1. HOTAIR was highly correlated with TNM (χ ² = 5.797, P = .016), tumor size (χ ² = 7.955, P = .005) and lymphatic metastasis (χ ² = 6.0, P = .014). HOTAIR promoted cell proliferation and inhibited cell apoptosis, whereas miR-761 did not. HOTAIR elevated and miR-761 suppressed PPME1 expression. HOTAIR expression appears to affect the survival time in vivo.

Conclusion: HOTAIR regulated thyroid cancer cells by binding to miR-761 through PPME1.

Keywords: HOTAIR; PPME1; miR‐761; thyroid cancer.