Circ_0000658 knockdown inhibits epithelial-mesenchymal transition in bladder cancer via miR-498-induced HMGA2 downregulation

Abstract

Background Epithelial-mesenchymal transition (EMT) has been associated with the angiogenesis and oncogenic phenotypes of multiple malignant tumors including bladder cancer (BCa). Circular RNAs (circRNAs) are recognized as crucial regulators in the EMT. This study aims to illustrate the possible role of circular RNA_0000658 (circ_0000658) in BCa and the underlying molecular mechanism. Methods The expression of circ_0000658, microRNA (miR)-498, and high mobility group AT-hook 2 (HMGA2) was assessed in cancer and adjacent normal tissue collected from BCa patients and human BCa cell lines (MGH-U3, T24, 5637 and SW780). BCa cells were transduced with a series of overexpression or shRNA plasmids to clarify the function of circ_0000658 and miR-498 on the oncogenic phenotypes and EMT of BCa cells. Further, we established nude mice xenografted with BCa cells to validate the roles of circ_0000658 on tumor growth in vivo. Results Circ_0000658 was highly expressed in BCa tissue samples and cell lines, which indicated a poor prognosis of BCa patients. Circ_0000658 competitively bound to miR-498 and thus restricted miR-498 expression. Meanwhile, circ_0000658 weakened the binding of miR-498 to the target gene HMGA2 and upregulated the HMGA2 expression. Circ_0000658 elevation or miR-498 knockdown augmented oncogenic phenotypes and EMT of BCa cells, corresponding to a reduction in the expression of β-catenin and E-cadherin as well as an increase in the expression of N-cadherin, Slug, Snail, ZEB1 and Twist. Inhibition of HMGA2 reversed the effects of circ_0000658 overexpression on tumor growth in vivo. Conclusion Altogether, our study uncovered the tumor-promoting role of circ_0000658 in BCa via the miR-498/HMGA2 axis.

Depletion of circ_0088046 suppressed cell growth and motility of hepatocellular carcinoma via circ_0088046‐miR‐1299‐RTKN2 ceRNA pathway

“…24 Circ_0000658 acted as a tumour-promoting factor in bladder cancer via regulating the miR-498/HMGA2 axis. 25 Circ CUL2 served as an antitumor factor to facilitate PPP6C expression and colorectal cancer progression via absorbing miR-208a-3p. 26 Moreover, the roles of circRNAs in the HCC process have been revealed.…”

“…With the development and application of RNA sequencing technology, a variety of abnormally expressed circRNAs have been discovered, and further study has found that they play an important role in cancer progression 24 . Circ_0000658 acted as a tumour‐promoting factor in bladder cancer via regulating the miR‐498/HMGA2 axis 25 . Circ CUL2 served as an antitumor factor to facilitate PPP6C expression and colorectal cancer progression via absorbing miR‐208a‐3p 26 .…”

Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer

“…reported that circST6GALNAC6, modulated by the transcription factor SP1, inhibits BCa metastasis through binding miR-200a-3p to regulate the STMN1/EMT axis ( 48 ), and Su et al. revealed that Circ_0000658 enhanced BCa cell proliferative, migratory and invasive capacities by miR-498/HMGA2/EMT signaling axis ( 49 ). As reported, circCEP128 promotes BCa progression through activating MAKP signaling pathway via miR-145-5p/MYD88 path ( 50 ).…”

Competitive adsorption of microRNA-532-3p by circular RNA SOD2 activates Thioredoxin Interacting Protein/NLR family pyrin domain containing 3 pathway and promotes pyroptosis of non-alcoholic fatty hepatocytes

“…The interaction between miR-532-3p and TXNIP protein was determined using an RIP kit (Millipore, Billerica, MA) [ 22 ]. Lysed cells were centrifuged to collect the supernatant.…”