CircVAMP3: A circRNA with a Role in Alveolar Rhabdomyosarcoma Cell Cycle Progression

Abstract

Circular RNAs (circRNAs), a class of covalently closed RNAs formed by a back-splicing reaction, have been involved in the regulation of diverse oncogenic processes. In this article we describe circVAMP3, a novel circular RNA overexpressed in RH4, a representative cell line of alveolar rhabdomyosarcoma. We demonstrated that circVAMP3 has a differential m6A pattern opposed to its linear counterpart, suggesting that the two isoforms can be differently regulated by such RNA modification. Moreover, we show how circVAMP3 depletion in alveolar rhabdomyosarcoma cells can impair cell cycle progression, through the alteration of the AKT-related pathways, pointing to this non-coding RNA as a novel regulator of the alveolar rhabdomyosarcoma progression and as a putative future therapeutic target.

Emerging functions of circular RNA in the regulation of adipocyte metabolism and obesity

“…circRNAs are a class of covalently enclosed endogenous biomolecules that were first discovered in 1976 [ 20 ]. circRNAs play important roles in the growth or development of tissues and organs, as they are involved in cell cycle regulation, cell proliferation, and apoptosis in different tissues or organs [ 21 – 25 ]. In the past few years, the biosynthesis and molecular functions of circRNAs have been extensively explored and verified.…”

Non-coding RNA in rhabdomyosarcoma progression and metastasis

“…Another circRNA, circVAMP3, is significantly overexpressed in ARMS Rh4 cells compared to both normal myoblasts and the ERMS RD cell line ( 162 ). It was detected as both the circular and linear isoforms with the former being particularly more interesting to study in Rh4 cells because its upregulation was more prominent.…”

“…CircVAMP3 knockdown was shown to act through the alteration of the AKT-related pathway, and several AKT-pathway related genes were significantly deregulated such as AKT1 levels that were downregulated in siRNA-treated (si-circVAMP3) Rh4 cells compared to those treated with scrambled control. Furthermore, levels of the downstream inhibitors of the G2/M transition, the WEE1 and CDKN1A factors increased upon circVAMP3 knock-down ( 162 ).…”

Emerging Role and Mechanism of circRNAs in Pediatric Malignant Solid Tumors

“…In contrast, the knockdown of circ-ZNF609 had no significant effect on ARMS-derived cells but the exact reason for this is unclear ( Rossi et al, 2019 ). Circ-VAMP3 expression is significantly increased in ARMS cells, and knockdown of circVAMP3 regulates the CCNB1/CDK1 complex, which controls the G2/M checkpoint by promoting the expression of CDKN1A and WEE1, thus the AKK1 and CDK1 complexes, as well as downregulation of Akt and ERK1, thereby inhibiting the cell cycle ( Rossi et al, 2021 ).…”