CircSEC24A upregulates TGFBR2 expression to accelerate pancreatic cancer proliferation and migration via sponging to miR-606

Yankun Chen,Xueyi Jiang,Simiao Xu,Jianxin Jiang,Xinyuan Liu

doi:10.1186/s12935-021-02392-y

Abstract

BackgroundCircular RNA (circRNA), producing by special selective splicing, was widely expressed in the cytoplasm of eukaryotic cells as a newly non-coding RNAs. It played different roles in a variety of diseases including cancer and performed different functions. Nonetheless, reports on the specific function of circRNA in pancreatic cancer (PC) were still rarely so far. In particular, the role of circSEC24A in PC remains unclear.MethodsReal-time fluorescent quantitative PCR was used to evaluate the expression level of circSEC24A in pancreatic cancer tissues and cell lines. Furthermore, we used some functional experiments, such as EDU and Transwell assays, to explore the effects of circSEC24A on the proliferation and invasiveness of pancreatic cancer. Finally, the corresponding relationship among circSEC24A, miR-606 and TGFBR2 was explored by dual luciferase reporter and other mechanism studies.ResultsThe expression of circSEC24A in both pancreatic cancer tissues and cell lines was evidently up-regulated. Furthermore, knockdown of circSEC24A significantly inhibited the proliferative, migration and invasive capacity of pancreatic cancer cells, whereas miR-606 inhibitor obviously counteracted these effects. Further study confirmed that circSEC24A alleviated suppression on target TGFBR2 expression by directly sponging miR-606 and then influenced the tumorigenesis of pancreatic cancer.ConclusionsThese findings indicated that the progression of pancreatic cancer can be driven by circSEC24A influencing miR-606/TGFBR2 axis. Therefore, circSEC24A might be used as a critical biomarker influencing the early diagnosis and prognosis of pancreatic cancer.

Highlights

Circular RNA, producing by special selective splicing, was widely expressed in the cytoplasm of eukaryotic cells as a newly non-coding RNAs
CircSEC24A is highly expressed in pancreatic cancer To explore the expression profiles of circRNA in pancreatic cancer, we performed bioinformatics methods to screen differentially expressed circRNA based on GEO database via R software using “limma” and “heatmap” packages
PCR analysis suggested that circSEC24A was significantly highly expressed in pancreatic cancer tissues compared with their paired adjacent normal tissues (Fig. 1B)

Summary

Introduction

Circular RNA (circRNA), producing by special selective splicing, was widely expressed in the cytoplasm of eukaryotic cells as a newly non-coding RNAs. There is increasing evidence that circRNAs participate in multiple biological functions in tumors, including cell proliferation, apoptosis, differentiation, metastasis and regulation of gene expression [7]. Previous study suggested that circCDR1as was overexpressed in pancreatic cancer and promoted the proliferation, migration and invasion of pancreatic cancer cells by regulating E2F3 expression via functioning as sponge for miR-432-5p [11]. Inhibitory expression of circ_0013912 significantly suppressed pancreatic cancer cell proliferation and metastasis via sponging miR-7-5p [12]. Zhang et al declared that circ_001587 elevated SLC4A4 expression to suppress malignant phenotype of pancreatic cancer, including angiogenesis and metastasis. Deep exploration of the circRNA-miRNA-mRNA network for pancreatic cancer is benefited for excavating novel biomarkers for diagnosis and treatment of pancreatic cancer

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Discussion

Conclusion