The competing endogenous circular RNA ADAMTS14 suppressed hepatocellular carcinoma progression through regulating microRNA‐572/regulator of calcineurin 1

Abstract

Emerging evidence have discovered that circular RNAs (circRNAs) may serve as diagnostic or tumor promising biomarkers. This study aimed to investigate how circular RNA ADAMTS14 (circADAMTS14) regulates microRNA‐572/ regulator of calcineurin 1(miR‐572/ RCAN1) in hepatocellular carcinoma (HCC). The expression profiles of circRNA/microRNA (mRNA) between HCC tissues and paired adjacent tissues were analyzed via microarray analysis. The expressions of circADAMTS14, miR‐572, and RCAN1 were measured by real‐time polymerase chain reaction (PCR). The protein expression level of RCAN1 in HCC cells was detected by western blot. The viability and apoptosis levels of HCC cell lines were measured by the cell counting Kit‐8 (CCK‐8) assay and fluorescence‐activated cell sorter. The invasiveness and migration of cells were detected based on the transwell and wound‐healing assay, respectively. The dual‐luciferase reporter assays were used to reveal circADAMTS14 and RCAN1 as a potential target of miR‐572, which was predicted by TargetScan and miRBase. The effect of circADAMTS14 on HCC cells was demonstrated by tumor formation in nude mice in vivo. CircADAMTS14 and RCAN1 were lowly expressed in HCC clinical specimens and cell lines using microarrays and qRT‐PCR, but miR‐572 inversely. Our study further verified the direct interaction between circADAMTS14 and RCAN1 with miR‐572 via the dual‐luciferase reporter gene assay. Overexpressed circADAMTS14 and RCAN1 induced apoptosis of HCC cells and inhibited cell proliferation and invasion. But overexpressed miR‐572 could decrease apoptosis of HCC cells and promote proliferation and invasion. In vivo, circADAMTS14 inhibited the tumor growth, correlated positively with the protein expression levels of RCAN1. Our results demonstrated that circADAMTS14 might suppress HCC progression through regulating miR‐572/ RCAN1 as the competing endogenous RNA.

Decreased Cytoplasmic Expression of ADAMTS14 Is Correlated with Reduced Survival Rates in Oral Squamous Cell Carcinoma Patients

“…SP1-related transcriptional regulation of ADAMTS3 gene expression in osteosarcoma cell models [54]. Furthermore, the competing endogenous circular ADAMTS14 might suppress HCC progression through regulating miR-572/RCAN1 as the competing endogenous RNA [55]. Nonetheless, to the best of our knowledge, this is the first study to investigate the role of ADAMTS14 protein expression in OSCC and also the first study to investigate the association between ADAMTS14 protein expression and other clinicopathological features of OSCC.…”

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 .…”

Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients

“…Recent evidences have suggested that circRNAs involve in far‐ranging biological processes, including transcription, mRNA splicing, RNA decay and translation, and their deregulation takes pivotal roles in the development and metastasis of various tumors, such as glioma, 15 hepatoblastoma, 16 colorectal cancer, 17 lung cancer, 18 prostate cancer, 19 bladder cancer, 20 and gastric cancer 21 . For example, Li et al revealed that circANKS1B promotes colorectal cancer cell migration and invasion by working as a molecular sponge of miR‐149 to regulate FOXM1 and Slug protein expressions 17 .…”