Hsa_circ_0043265 Restrains Cell Proliferation, Migration and Invasion of Tongue Squamous Cell Carcinoma via Targeting the miR-1243/SALL1 Axis.

Yisheng Yang,Tianchen Lan,Cuijuan Qian,Jun Yao,Yichao Wang

doi:10.3389/pore.2021.587130

Yisheng Yang, Tianchen Lan + Show 3 more

Open Access

https://doi.org/10.3389/pore.2021.587130

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Abstract

Increasing evidence has displayed critical roles of circular RNAs (circRNAs) in tongue squamous cell carcinoma (TSCC). Hsa_circ_0043265 (circ_0043265) has been identified as a tumor suppressor in various tumors. Nevertheless, the critical roles of circ_0043265 in the initiation and progression of TSCC are yet to be fully elucidated. In our study, RNA and protein expressions were detected via qRT-PCR and Western blot. Cell proliferation, migration and invasion were evaluated via CCK-8 and transwell assays. The interactions between circ_0043265, miR-1243 and SALL1 were analyzed via bioinformatics analyses, RNA pull-down and luciferase assays, respectively. The current study demonstrated that circ_0043265 expression was downmodulated in TSCC tissues and cell lines (SCC25, SCC15, SCC9 and Cal27). Functionally, circ_0043265 overexpression led to an attenuation of cell proliferation, migration and invasion of SCC25 and Cal27 cells. Mechanistically, circ_0043265 acted as a competing endogenous RNA (ceRNA) via competitively sponging miR-1243, and restoration of miR-1243 rescued the inhibitory effects of circ_0043265 on cell proliferation, migration and invasion of SCC25 and Cal27 cells. Finally, it was observed that spalt like transcription factor 1 (SALL1), a potential target of miR-1243, was positively modulated via circ_0043265 in SCC25 and Cal27 cells, and SALL1 knockdown reversed the inhibitory effects of circ_0043265 on SCC25 and Cal27 cells. Collectively, the current study demonstrated that circ_0043265 was downmodulated in TSCC and was identified as a ceRNA that restrained the cell proliferation, migration and invasion of SCC25 and Cal27 cells via modulating the miR-1243/SALL1 axis.

Highlights

Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors in head and neck region, and is characterized via a high rate of regional lymph node metastasis and recurrence [1]
It was demonstrated that the overall survival (OS) of the TSCC patients exhibiting high circ_0043265 levels was significantly higher compared with those with low circ_0043265 levels (Figure 1B)
We found that miR-1243 may bind to the 3′-untranslated region (UTR) region of spalt like transcription factor 1 (SALL1) (Figure 3A)

Summary

Introduction

Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors in head and neck region, and is characterized via a high rate of regional lymph node metastasis and recurrence [1]. Increasing evidence has demonstrated that aberrant expression of circRNAs is implicated in the initiation and progression of various tumors, where they can act as oncogenes or tumor suppressors [5,6]. CircRNAs are involved in the modulation of the expression and function of downstream target genes, either posttranscriptionally or via chromatin modulation in TSCC initiation and progression [7,8,9,10,11]. Only a small number of circRNAs have been functionally characterized in TSCC at present, and the mechanisms underlying their biological functions are yet to be fully elucidated. The expression profile, clinical significance, biological function and mechanism of circ_0043265 in TSCC have not been fully investigated

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