Circular RNA circBACH2 plays a role in papillary thyroid carcinoma by sponging miR-139-5p and regulating LMO4 expression

Xiaoyan Cai,Jiangqi Liu,Zheng Zhao,Jie Kang,Yan Shen,Jiangnan Dong,Jun Li,Bei Yun,Qiang Lv

doi:10.1038/s41419-019-1439-y

Abstract

Circular RNAs (circRNAs) are a class of non-coding RNAs that are broadly expressed in various biological cells and function in regulating gene expression. They are structurally stable and tissue-specific. However, the function of human circRNAs and the role of circRNAs in papillary thyroid carcinoma (PTC) remain to be determined. Herein, the function of circRNA circBACH2 was investigated in human PTC cells. First, we detected the expression of circBACH2 in PTC tissues and PTC cell lines by RT-PCR. FISH was used to confirm the subcellular localization of circBACH2. A luciferase reporter assay and AGO2-RIP was used to confirm the relationship between circBACH2 and miR-139-5p. PTC cells were stably transfected with siRNA against circBACH2 and cell proliferation, migration and invasion were detected to evaluate the effect of circBACH2 in PTC, while tumorigenesis was assayed in nude mice. We found that circBACH2 was highly expressed in PTC tissues and PTC cell lines. Mechanistically, we confirmed that circBACH2 could directly bind to miR-139-5p and relieve suppression of the target LMO4. Functionally, we found that inhibiting circBACH2 expression decreased cell proliferation, migration, and invasion. Finally, down-regulating circBACH2 suppressed the growth of PTC xenografts in nude mice. Our findings indicate that circBACH2 acts as a novel oncogenic RNA that sponges miR-139-5p and can be used as a tumor biomarker of PTC. What’s more, these results revealed that the circBACH2/miR-139-5p/LMO4 axis could be targeted as a potential treatment strategy for PTC.

Highlights

Thyroid cancer is one of the fastest growing malignant tumors in the world, as its global incidence has tripled over the past 30 years[1]
Results circBACH2 is highly expressed in papillary thyroid carcinoma (PTC) tissues and PTC cell lines
We used the ROC curve to examine the diagnostic value of circBACH2 in PTC tissues compared with paratumor tissues, and found the area under the ROC curve (AUC) to be 0.8631

Summary

Introduction

Thyroid cancer is one of the fastest growing malignant tumors in the world, as its global incidence has tripled over the past 30 years[1]. Circular RNA (circRNA) is a class of non-coding RNA that is broadly found in mammals. It is mainly involved in gene regulation in vivo[8,9,10]. Several circRNAs have been found to contain at least one miRNA binding site They can be used as RNA “sponges” to adsorb miRNAs, thereby regulating the expression of downstream target genes that are inhibited by miRNAs through the mechanism of competing endogenous RNAs13. The use of circRNAs as miRNA “sponges” to regulate downstream target genes has been widely reported[14,15,16]. The regulatory roles of circBACH2 and its potential role as an “miRNA sponge” in PTC are still largely unclear

Methods

Results

Conclusion