Circ_0000140 restrains the proliferation, metastasis and glycolysis metabolism of oral squamous cell carcinoma through upregulating CDC73 via sponging miR-182-5p

Jia Guo,Meng Zhang,Yuanyuan Su

doi:10.1186/s12935-020-01501-7

Jia Guo, Meng Zhang + Show 1 more

Open Access

https://doi.org/10.1186/s12935-020-01501-7

Copy DOI

Abstract

BackgroundOral squamous cell carcinoma (OSCC) is a more common cancer in the world. Emerging evidence suggests that circular RNAs (circRNAs) participate in the progression of OSCC. However, the role of circ_0000140 in OSCC is still unknown.MethodsThe expression of circ_0000140 and microRNA-182-5p (miR-182-5p) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Also, cell proliferation, migration and invasion were measured by colony formation and transwell assays, respectively. Western blot (WB) analysis was used to test the levels of proliferation, metastasis and glycolysis metabolism-related proteins as well as cell division cycle 73 (CDC73) protein. Further, the extracellular acidification rate (ECAR) of cells was detected by the Seahorse XF Extracellular Flux Analyzer. The lactate acid level of cells was tested by Lactate Assay Kit. Moreover, dual-luciferase reporter was used to verify the interaction between miR-182-3p and circ_0000140 or CDC73, and RNA immunoprecipitation (RIP) assay was employed to further confirm the relationship between miR-182-3p and circ_0000140. In addition, mice xenograft models were built to measure the effect of circ_0000140 on OSCC tumor growth in vivo.ResultsCirc_0000140 was lowly expressed in OSCC, and its overexpression hindered proliferation, migration, invasion and glycolysis metabolism in OSCC cells. MiR-182-5p could be sponged by circ_0000140, and its mimic could invert the suppression of circ_0000140 overexpression on OSCC progression. CDC73 could be targeted by miR-182-3p, and its silencing could reverse the inhibition of miR-182-3p inhibitor on OSCC progression. Further, overexpressed circ_0000140 reduced the OSCC tumor growth in vivo.ConclusionsCirc_0000140 might play an anti-cancer role in OSCC, which provided a novel target for clinical therapy of OSCC.

Highlights

Oral squamous cell carcinoma (OSCC) is a more common cancer in the world
The results showed that circ_0000140 could resist the action of Ribonuclease R (RNase R), while linear RNA KIAA0907 could be digested by RNase R, indicating that circ_0000140 was circular (Fig. 1d, e)
The results indicated that miR-182-5p expression was inhibited by circ_0000140 overexpression in OSCC cells (Fig. 4g)

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is a more common cancer in the world. Oral squamous cell carcinoma (OSCC) is a common type of oral cancer and belongs to the category of malignant tumors [1, 2]. Many studies have demonstrated that circRNAs can be involved in the proliferation and metastasis of cancer cells to play a pro-cancer or anticancer effect in cancer progressions, such as circFMN2, circFBXL5 and circGRAMD18 [8,9,10]. Circ_0000140 is a newly discovered circRNA with significantly low expression in OSCC patients [13]. A recent study had shown that low circ_0000140 expression was significantly associated with the poor prognosis in OSCC patients and could function as a potential biomarker for OSCC [14]. Circ_0000140 might be an important target for the treatment of OSCC, and its role and mechanism in the progression of OSCC deserved further investigation

Methods

Results

Discussion

Conclusion