CircSSU72 Promotes Cell Proliferation, Migration and Invasion of Papillary Thyroid Carcinoma Cells by Targeting miR-451a/S1PR2 Axis.

Zeyu Zhang,Bo Jiang,Fada Xia,Lei Yao,Xinying Li

doi:10.3389/fcell.2022.817028

Abstract

Introduction: Thyroid cancer is the most common endocrine malignancy with Papillary Thyroid Carcinoma (PTC) as the most common pathological type. Due to low mortality but a high incidence, PTC still causes a relatively heavy burden on financial costs, human health, and quality of life. Emerging researches have indicated that circular RNAs (circRNAs) play a significant regulatory role in various cancers, including PTC. However, the functions and mechanisms of circRNAs derived from SSU72 remain unknown. Method: The expression level of circRNAs derived from the exons of SSU72, miR-361–3p, miR-451a, and S1PR2 was evaluated by qRT-PCR assay or western blot assay. The interactions between circSSU72 (hsa_circ_0009294), miR-451a, and S1PR2 were verified by dual-luciferase reporter assay. Effects of circSSU72, miR-451a, and S1PR2 on cell proliferation, migration, and invasion were confirmed by colony formation assay, cell counting kit-8 (CCK-8), wound healing assay, and Transwell assays in vitro. Results: circSSU72 was upregulated in PTC; circSSU72 knockdown inhibited PTC cell proliferation, migration, and invasion. In addition, circSSU72 could negatively regulate miR-451a by functioning as a sponge. circSSU72 promoted PTC cell proliferation, migration, and invasion by targeting miR-451a in vitro. We further found that miR-451a inhibited PTC cell proliferation, migration, and invasion by regulating S1PR2. Overall, the circSSU72/miR-451a/S1PR2 axis might influence PTC cell proliferation, migration, and invasion. Conclusions: Overall, circSSU72 (hsa_circ_0009294)/miR-451a/S1PR2 axis may promote cell proliferation, migration, and invasion in PTC. Thus, circSSU72 may serve as a potential biomarker and therapeutic target for PTC.

Highlights

Thyroid cancer is the most common endocrine malignancy with Papillary Thyroid Carcinoma (PTC) as the most common pathological type
SSU72 physiologically functions as a cohesin-binding phosphatase, but is involved in various diseases, including nonalcoholic steatohepatitis, hepatocellular carcinoma, and autoimmune diseases. (Hwang et al, 2021) SSU72 shows the highest expression in the thyroid among all the normal tissues. (Fagerberg et al, 2014) we consider that the SSU72-derived circRNAs may participate in the oncogenesis and development of papillary thyroid carcinoma (PTC)
Wound healing assay and Transwell invasion and migration assay revealed the suppressive effects of si-circSSU72 on the ability of invasion and migration of TPC-1 (Figures 4E,F) and IHH-4 cells (Supplementary Figure S2) could be reversed by miR-451a inhibiting. These results indicated that circSSU72 affected the proliferation, migration, and invasion of PTC cells by targeting miR-451a

Summary

Introduction

Thyroid cancer is the most common endocrine malignancy with Papillary Thyroid Carcinoma (PTC) as the most common pathological type. (DeGroot et al, 1990; Sebastian et al, 2000; Laha et al, 2020) Due to the low mortality but the high incidence, PTC still causes a relatively heavy burden on financial costs, human health, and quality of life. CircRNAs usually function as competitive endogenous RNAs (ceRNAs) by sponging micro RNAs (miRNAs), influencing mRNAs expression and further oncogenesis and development of diseases. SSU72 has a unique active site with specific structural characteristics at the C-terminus. It consists of a central 5-stranded β-sheet (β1–β5) enclosed by helices on both sides. (Fagerberg et al, 2014) we consider that the SSU72-derived circRNAs may participate in the oncogenesis and development of PTC SSU72 physiologically functions as a cohesin-binding phosphatase, but is involved in various diseases, including nonalcoholic steatohepatitis, hepatocellular carcinoma, and autoimmune diseases. (Hwang et al, 2021) SSU72 shows the highest expression in the thyroid among all the normal tissues. (Fagerberg et al, 2014) we consider that the SSU72-derived circRNAs may participate in the oncogenesis and development of PTC

Methods

Results

Discussion

Conclusion