10.6084/M9.FIGSHARE.C.6235101.V1
Yongzhen Mo
Yongzhen
Mo
Central South University
Yumin Wang
Yumin
Wang
Xiangya Hospital Central South University
Yian Wang
Yian
Wang
Central South University
Xiangying Deng
Xiangying
Deng
Central South University
Qijia Yan
Qijia
Yan
Xiangya Hospital Central South University
Chunmei Fan
Chunmei
Fan
Central South University
Shuai Zhang
Shuai
Zhang
Xiangya Hospital Central South University
Shanshan Zhang
Shanshan
Zhang
Xiangya Hospital Central South University
Zhaojian Gong
Zhaojian
Gong
Second Xiangya Hospital of Central South University
Lei Shi
Lei
Shi
Second Xiangya Hospital of Central South University
Qianjin Liao
Qianjin
Liao
Central South University
Can Guo
Can
Guo
Central South University
Yong Li
Yong
Li
Baylor College of Medicine
Guiyuan Li
Guiyuan
Li
Central South University
Zhaoyang Zeng
Zhaoyang
Zeng
Central South University
Weihong Jiang
Weihong
Jiang
Xiangya Hospital Central South University
Wei Xiong
Wei
Xiong
Central South University
Bo Xiang
Bo
Xiang
Central South University
Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop
Abstract Background Circular RNAs (circRNAs) act as gene expression regulators and are involved in cancer progression. However, their functions have not been sufficiently investigated in nasopharyngeal carcinoma (NPC). Methods The expression profiles of circRNAs in NPC cells within different metastatic potential were reanalyzed. Quantitative reverse transcription PCR and in situ hybridization were used to detect the expression level of circPVT1 in NPC cells and tissue samples. The association of expression level of circPVT1 with clinical properties of NPC patients was evaluated. Then, the effects of circPVT1 expression on NPC metastasis were investigated by in vitro and in vivo functional experiments. RNA immunoprecipitation, pull-down assay and western blotting were performed to confirm the interaction between circPVT1 and β-TrCP in NPC cells. Co-immunoprecipitation and western blotting were performed to confirm the interaction between β-TrCP and c-Myc in NPC cells. Results We find that circPVT1, a circular RNA, is significantly upregulated in NPC cells and tissue specimens. In vitro and in vivo experiments showed that circPVT1 promotes the invasion and metastasis of NPC cells. Mechanistically, circPVT1 inhibits proteasomal degradation of c-Myc by binding to β-TrCP, an E3 ubiquiting ligase. Stablization of c-Myc by circPVT1 alters the cytoskeleton remodeling and cell adhesion in NPC, which ultimately promotes the invasion and metastasis of NPC cells. Furthermore, c-Myc transcriptionally upregulates the expression of SRSF1, an RNA splicing factor, and recruits SRSF1 to enhance the biosynthesis of circPVT1 through coupling transcription with splicing, which forms a positive feedback for circPVT1 production. Conclusions Our results revealed the important role of circPVT1 in the progression of NPC through the β-TrCP/c-Myc/SRSF1 positive feedback loop, and circPVT1 may serve as a prognostic biomarker or therapeutic target in patients with NPC.
Biophysics
Biochemistry
Cell Biology
Genetics
Molecular Biology
Physiology
Immunology
Biological Sciences not elsewhere classified
Developmental Biology
Cancer
Computational Biology
figshare
2022
2022-10-06
2022-10-06
Collection
10.6084/m9.figshare.c.6235101
CC BY 4.0