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

Abstract

Background/Aims: We aimed to study the involvement of circZMYM2 (hsa_circ_0099999) in pancreatic cancer (PC) cell proliferation, apoptosis and invasion and to figured out the underlying mechanism of circZMYM2 regulating miR-335-5p and JMJD2C. Methods: CircRNA differential expressions in twenty PC samples and paired normal tissue samples were analyzed using Arraystar Human CircRNA microarray V1. CircZMYM2 expression level was determined via qRT-PCR. The effects of circZMYM2 inhibition and overexpression on cell proliferation, cell apoptosis and cell invasion were investigated by CCK-8 assays, Flow cytometry assays and Transwell assays. An animal experiment on nude mice was put forward to test the influence of circZMYM2 knockdown on tumor growth. The relationship between circZMYM2, miR-335 and JMJD2C was verified by RNA pull down, dual-luciferase reporter assays and rescue experiment. The effect of circZMYM2 and miR-335-5p on the expression of JMJD2C protein was detected by western blot. Results: CircZMYM2 overexpression was observed in both PC tissues and cells. Knockdown of circZMYM2 inhibited proliferation, induced apoptosis, and weakened invasion ability of cancer cells. Tumor growth was restrained in vivo. CircZMYM2 repressed the expression of its target miR-335-5p. MiR-335-5p attenuated pancreatic cancer development via inhibition of JMJD2C. Conclusion: Our study demonstrated that circZMYM2 promoted PC progression. CircZMYM2 had a sponge effect on miR-335-5p and modulated the downstream oncogene JMJD2C.

Non-coding RNAs in Pancreatic Ductal Adenocarcinoma

“…An additional study also revealed that circ_0007534 functions as a sponge for miR-625 and miR-892b to facilitate the malignant behavior of PDAC cells (82). Studies have identified that circZMYM2 (hsa_circ_0099999) is up-regulated in both PDAC cells and tissues, promoting tumor progression by influencing JMJD2C expression levels via acting as miR-355-5p sponges (84).…”

Construction of a circRNA‐miRNA‐mRNA network to explore the pathogenesis and treatment of pancreatic ductal adenocarcinoma

“…3 Competing endogenous RNAs (ceRNAs) compete with other RNAs for the seed region of shared miRNAs, thus modulating the activity of the miRNAs. 9,10 However, many circRNAs still need to be discovered. [4][5][6] Recently, it has been reported that abundant conserved miRNA response elements (MREs) exist in circRNAs, 7 making circRNAs a hot topic in ceRNA family research.…”

“…8 circRNAs have also been reported to mediate the pathological process in pancreatic ductal adenocarcinoma (PDAC) via a mechanism involving ceRNAs. 9,10 However, many circRNAs still need to be discovered.…”

CircFOXK2 Promotes Tumor Growth and Metastasis of Pancreatic Ductal Adenocarcinoma via Complexing with RNA Binding Proteins and Sponging MiR-942

“…circITCH absorbed miR-17 and miR-224 to promote p21 and PTEN expression in bladder cancer 26 . ciRS-7 targeted miR-7 to promote EGFR/STAT3 signaling, while circZMYM2 sponged miR335-5p and in turn favored the expression of JMJD2C in PDAC 27,28 . Here, we performed bioinformatics analysis, luciferase assay and miRNA pull down assay to identify circFOXK2-interacting miRNAs in PDAC cells.…”