CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway

Abstract

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that play an important role in cancer. However, the mechanisms by which circRNAs regulate gene expression in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study seeks to elucidate the role that circRNAs play in the proliferation of PDAC cells. On the basis of previous studies of circRNA expression profiles in PDAC, we found that the circRNA_100782 was markedly upregulated in PDAC tissue. Functional experiments revealed that circRNA_100782 down-regulation inhibited BxPC3 cell proliferation and colony formation. Loss-of-function studies showed that knockdown of circRNA_100782 inhibited cell proliferation by downregulating the microRNA-124 (miR-124) target genes interleukin-6 receptor (IL6R) and signal transducer and activator of transcription 3 (STAT3). Overexpression of miR-124 also inhibited BxPC3 cell proliferation by reducing the expression of IL6R and STAT3, which was consistent with the result of silencing circRNA_100782. In addition, luciferase assay revealed that miR-124 was a direct target of circRNA_100782. Silencing STAT3 inhibited BxPC3 cell proliferation and colony formation. Cell viability was reduced in BxPC3 cells treated with si-circRNA_100782 and miR-124 mimic, and this effect could be attenuated by activating STAT3. In vivo study validated that circRNA_100782 knockdown suppressed BxPC3 xenografts in nude mice. Taken together, these results suggest that circRNA_100782 regulates BxPC3 cell proliferation by acting as miR-124 sponge through the IL6–STAT3 pathway.

circZMYM2 Competed Endogenously with miR-335-5p to Regulate JMJD2C in Pancreatic Cancer

“…As was discovered by Yang et al, circLDLRAD3 was upregulated and was significantly associated with cell invasion and metastasis in PC [13]. Chen et al studied the circrna_100782 regulation through the IL6-STAT3 pathway on PC cell proliferation [14]. In the present study, circZMYM2 affects JMJD2C expression by miR-335.…”

Screening for functional circular RNAs using the CRISPR-Cas13 system

“…2a-c). siRNAs 5,16,17 and shRNAs 3,4 were used in loss-of-function (LOF) studies of circRNAs. We compared the specificity and knockdown efficiency of the RfxCas13d system and shRNAs in a position-matched manner for nine pairs of circular and linear cognate RNAs (Fig.…”

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

“…Moreover, many circRNAs are tissue‐specifically expressed, highly conserved, and can be detected in many kinds of body fluids . circRNA_100782 was markedly upregulated in pancreatic ductal adenocarcinoma tissue and regulated BxPC3 pancreatic cancer cells proliferation by acting as miR‐124 sponge through the IL6–STAT3 pathway . Functional experiments revealed circRNA_010567 silencing could upregulate miR‐141 and downregulate TGF‐β1 expression, play an important regulatory role in the diabetic mice myocardial fibrosis model, and suppress fibrosis‐associated protein resection in cardiac fibroblasts .…”

“…[40][41][42][43][44] circRNA_100782 was markedly upregulated in pancreatic ductal adenocarcinoma tissue and regulated BxPC3 pancreatic cancer cells proliferation by acting as miR-124 sponge through the IL6-STAT3 pathway. 45 Functional experiments revealed circRNA_010567 silencing could upregulate miR-141 and downregulate TGF-β1 expression, play an important regulatory role in the diabetic mice myocardial fibrosis model, and suppress fibrosis-associated protein resection in cardiac fibroblasts. 46 The systemic lupus erythematosus (SLE) is the prototypic human autoimmune disease characterized by the presence of autoantibodies against several self-antigens, which causes serious injury to various organs or systems.…”