Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis

By Yibing Yang, Xinya Gao, Maolei Zhang, Sheng Yan, Chengjun Sun, Feizhe Xiao, Nunu Huang, Xuesong Yang, Kun Zhao, Huangkai Zhou and 3 more. Journal of the National Cancer Institute, 2017

965 citations recorded by the source corpus.

Abstract Background Circular RNAs (circRNAs) are RNA transcripts that are widespread in the eukaryotic genome. Recent evidence indicates that circRNAs play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported. Methods CircRNA deep sequencing was performed by using 10 pathologically diagnosed glioblastoma samples and their paired adjacent normal brain tissues. Northern blotting, Sanger sequencing, antibody, and liquid chromatograph Tandem Mass Spectrometer were used to confirm the existence of circ-FBXW7 and its encoded protein in in two cell lines. Lentivirus-transfected stable U251 and U373 cells were used to assess the biological functions of the novel protein in vitro and in vivo (five mice per group). Clinical implications of circ-FBXW7 were assessed in 38 pathologically diagnosed glioblastoma samples and their paired periphery normal brain tissues by using quantitative polymerase chain reaction (two-sided log-rank test). Results Circ-FBXW7 is abundantly expressed in the normal human brain (reads per kilobase per million mapped reads [RPKM] = 9.31). The spanning junction open reading frame in circ-FBXW7 driven by internal ribosome entry site encodes a novel 21-kDa protein, which we termed FBXW7-185aa. Upregulation of FBXW7-185aa in cancer cells inhibited proliferation and cell cycle acceleration, while knockdown of FBXW7-185aa promoted malignant phenotypes in vitro and in vivo. FBXW7-185aa reduced the half-life of c-Myc by antagonizing USP28-induced c-Myc stabilization. Moreover, circ-FBXW7 and FBXW7-185aa levels were reduced in glioblastoma clinical samples compared with their paired tumor-adjacent tissues (P < .001). Circ-FBXW7 expression positively associated with glioblastoma patient overall survival (P = .03). Conclusions Endogenous circRNA encodes a functional protein in human cells, and circ-FBXW7 and FBXW7-185aa have potential prognostic implications in brain cancer.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f5655ba1db27f01a17bbfeb4eff18f248d8c6775

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Citations in the corpus

Non-coding RNAs in disease: from mechanisms to therapeutics (2023, positive): “Indeed, several circRNA-encoded proteins, such as FBXW7-185aa, SHPRH-146aa and PINT-87aa, were shown to suppress glioma tumorigenesis 85,132,133 .”
Circular RNA-protein interactions: functions, mechanisms, and identification (2020, background): “Known functions of circRNA-protein interactions. circRNAs Interacting proteins Biological functions Types of cell/tissue Cytoplasm/nucleus Ref. circFOXO3 P21,CDK2 inhibits cell cycle progression mouse fibroblast NIH3T3 cytoplasm [44] circFOXO3 ID-1,E2F1,FAK,HIF1α cardiac senescence cardiomyocytes/ca”
Past, present, and future of circRNAs (2019, positive): “In addition, Yang et al (2017) identified several small peptides generated from a subset of circRNAs in cancer cell lines and human fibroblasts (Yang et al , 2017).”
Circular RNAs: Promising Biomarkers for Human Diseases (2018, background): “Additionally, study on human U251 and U373 cell line has displayed a novel protein encoded form circ-FBXW7 [30]; and a novel tumor suppressive protein encoded by circ-SHPRH has been identified in glioblastoma [31].”
Circular RNA: metabolism, functions and interactions with proteins (2020, background): “Peptides encoded by circRNAs are generally truncated and their functions are mostly analogous to the fulllength protein counterparts (circFBXW7-185aa [23, 85]).”