Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinoma

Abstract

Circular RNA (circRNA) can participate in various biological processes, including tumorigenesis, through their microRNA response elements. Alterations in circRNA profiles during hepatocellular carcinoma (HCC) progression and their clinical significance remain unclear. Here, we present extensive analysis of circRNA profiles in tumor and matched peritumor tissues collected from 10 HCC patients, conducted to identify circRNA related to HCC progression. A total of 42 dysregulated circRNA (38 down‐regulated and 4 up‐regulated) were identified in HCC tumor tissues compared with matched peritumor tissues, revealing the heterogeneity of circRNA profiles in HCC. CircADAMTS13, derived from Exon 13–14 of the ADAMTS13 gene, was significantly downregulated in HCC tumor tissues. Furthermore, clinicopathological analysis revealed that up‐regulation of circADAMTS13 was negatively associated with tumor size but positively associated with prognosis. In addition, overexpression of circADAMTS13 could markedly inhibit HCC cell proliferation in vitro. Bioinformatic analysis and luciferase reporter assays further revealed that circADAMTS13 directly interacts with microRNA (miR)‐484. Rescue experiments showed that miR‐484 mimics can reverse the tumor‐suppressing roles of circADAMTS13 in HCC. Therefore, our results demonstrated that circADAMTS13 can serve as a tumor suppressor during HCC progression via the functional pathway of sponging miR‐484.

Comprehensive profiling of circular RNA expressions reveals potential diagnostic and prognostic biomarkers in multiple myeloma

“…With the rapid progression and wide application of high-throughput sequencing and microarray, the expression pattern of circRNAs in various human diseases are increasingly reported, and the dysregulated expressions of circRNAs are shown to contribute to the pathogenesis of various cancers [7,[9][10][11][14][15][16][17][18][19]. For instance, in hepatitis B-related HCC, 189 upregulated circRNAs and 37 downregulated circRNAs were found by circRNA microarray, and circRNA_100,338 is further validated to be associated with metastatic progression by acting as an endogenous sponge for miR-141-3p [7].…”

“…With the development of circRNA microarrays, our knowledge about circRNA expression patterns has been initially uncovered in various diseases. In cancer research, circRNA expression patterns have been studied in some solid tumors including breast cancer, esophageal squamous cell cancer, epithelial ovarian cancer, etc., and a number of circRNAs are disclosed to involve in the pathophysiological progression of these malignancies [8][9][10][11]. As for hematological malignancies, an extensive analysis of circRNA expression profiles reveals a total of 464 dysregulated circRNAs (147 upregulated and 317 downregulated) in acute myeloid leukemia (AML) patients compared with healthy controls, and among these circRNAs, circ_0004277 is validated to be positively associated with prognosis in AML patients [9].…”

Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets

“…CircADAMTS14, which is downregulated in the HCC cell line, acts as a sponge of miR‐572 to regulate the expression of RCAN1 and thereby inhibit HCC progression . It has also been found that circADAMTS13 acts as a tumor suppressor during HCC progression through a functional pathway as a miR‐484 sponge . Another study found that circMTO1 acts as a sponge of miR‐9 and then upregulates the expression of P21 and inhibits the progression of HCC .…”

Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2

“…In the molecular level, the roles of circRNAs in cancer development are mainly attributable to the alternation of miRNAs. CircRNA a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (circADAMTS13) inhibited cell proliferation in hepatocellular carcinoma by sponging miR-484 [31] and circRNA transferrin receptor (cTFRC) could sponge miR-107 to accelerate the evolvement of bladder cancer [32]. For circ_RPL23A in CCRCC, miR-1233 was identi ed as a target for circ_RPL23A and circ_RPL23A played an anti-carcinoma role in CCRCC through the functional pathway of sponging miR-1233.…”