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

Abstract

Background Circular 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. Methods Real-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. Results The 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. Conclusions These 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.

Dysregulation of the circ_0087502/miR-1179/TGFBR2 pathway supports gemcitabine resistance in pancreatic cancer

“…As a consequence, we used the Targetscan database to discover putative miR-1179 target genes. Although many candidate genes emerged, TGFBR2, a predicted target, stood out and was chosen for further analysis, based on previous reports showing that TGFBR2 overexpression increases PC cell proliferation, migration, invasion, and EMT 11 , 12 . Using the UALCAN ( Figure 6a ) and GEPIA databases ( Figure 6b ), we showed that in TCGA PC samples, TGFBR2 levels were increased in PC tissues compared to normal tissues.…”

“…When TGFBR2 expression was restored in miR-204-overexpressing gastric cancer cells, they regained resistance to 5-FU treatment 29 . Although previous reports showed that TGFBR2 functioned as a key oncogene to increase PC cell proliferation, migration, invasion, and EMT 11 , 12 , the roles of TGFBR2 in gemcitabine sensitivity in PC are still unknown. In the current work, we reported that TGFBR2 overexpression dramatically induced proliferation, migration, invasion, and gemcitabine resistance in PC cells.…”

“…TGFBR2 was known to activate the downstream TGF-β signaling during tumorigenesis 25 . It has been demonstrated that TGFBR2 is dysregulated in a variety of human malignancies, including breast cancer 26 , colorectal cancer 27 , prostate cancer 28 , and PC 11 , 12 . Interestingly, TGFBR2 was identified as a direct target of miR-204 in gastric cancer cells, where miR-204 overexpression inhibited gastric cancer cell growth, invasion, and migration, and sensitized gastric cancer cells to 5-FU in vitro 29 .…”

CircRNAs: Pivotal modulators of TGF-β signalling in cancer pathogenesis

“…It decreased cell proliferation, migration, and invasion, making gemcitabine more effective as shown in Fig. 2 [ 76 ]. In the complex world of gene regulation, circular RNAs (circRNAs) like circEIF3I are crucial.…”

CircSEC24A (hsa_circ_0003528) interference suppresses epithelial-mesenchymal transition of hepatocellular carcinoma cells via miR-421/MMP3 axis

“…More importantly, alterations affecting circRNA expression have been reported to be linked to EMT to modulate tumor metastatic behavior [ 20 , 21 ]. circSEC24A is a newfound circRNA that has been reported to accelerate tumor progress in squamous cell carcinoma [ 22 ] and pancreatic cancer [ 23 ]. However, the function of circSEC24A in HCC is indistinct.…”