Autophagy-associated circular RNA hsa_circ_0007813 modulates human bladder cancer progression via hsa-miR-361-3p/IGF2R regulation

Circular RNAs (circRNAs) drive several cellular processes including proliferation, survival, and differentiation. Here, we identified a circRNA hsa_circ_0007813, whose expression was upregulated in bladder cancer. High hsa_circ_0007813 expression was associated with larger tumor size, higher primary...

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Veröffentlicht in:Cell death & disease Jg. 12; H. 8; S. 778 - 11
Hauptverfasser: Zhang, Zheyu, Mou, Zezhong, Xu, Chenyang, Wu, Siqi, Dai, Xiyu, Chen, Xinan, Ou, Yuxi, Chen, Yiling, Yang, Chen, Jiang, Haowen
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 07.08.2021
Springer Nature B.V
Nature Publishing Group
Schlagworte:
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Animals
Antibodies
Autophagy
Autophagy - genetics
Base Sequence
Biochemistry
Biomedical and Life Sciences
Bladder cancer
Cancer
Cell Biology
Cell Culture
Cell Line, Tumor
Cell proliferation
Cell Proliferation - genetics
Circular RNA
Disease Progression
Gene Expression Regulation, Neoplastic
Gene Silencing
HEK293 Cells
Humans
Immunology
Insulin-like growth factor II receptors
Invasiveness
Life Sciences
Male
Mannose
Medical prognosis
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs - genetics
MicroRNAs - metabolism
Neoplasm Invasiveness
Phagocytosis
Phagosomes - metabolism
Prognosis
Receptor, IGF Type 2 - metabolism
Ribonucleic acid
RNA
RNA, Circular - genetics
RNA, Circular - metabolism
RNA, Small Interfering - metabolism
Survival analysis
Tumor cells
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - pathology
ISSN:2041-4889, 2041-4889
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Zusammenfassung:Circular RNAs (circRNAs) drive several cellular processes including proliferation, survival, and differentiation. Here, we identified a circRNA hsa_circ_0007813, whose expression was upregulated in bladder cancer. High hsa_circ_0007813 expression was associated with larger tumor size, higher primary tumor T stage, and higher pathologic grade. Survival analysis showed that patients with high hsa_circ_0007813 expression levels had a poorer prognosis. Based on these findings from clinical tissue samples and cell lines, we assumed that hsa_circ_0007813 functioned a vital role in bladder cancer progression. Next, functional experiments revealed that knockdown of hsa_circ_0007813 inhibited proliferation, migration, and invasiveness of bladder cancer cells both in vitro and in vivo. Through extensive bioinformatic prediction and RNA pull-down assays, we identified hsa-miR-361-3p as a competing endogenous RNA of hsa_circ_0007813. Further bioinformatic studies narrowed targets to 35 possible downstream genes. We then found that knockdown of hsa_circ_0007813 led to altered cell autophagy, bringing our attention to IGF2R, one of the possible downstream genes. IGF2R was also known as cation-independent mannose-6-phosphate receptor (CI-M6PR), was discovered to participate in both autophagy and tumor biology. Regarding autophagy has a dominant role in the survival of tumor cells overcoming cellular stress and correlates with tumor progression, investigations were made to prove that hsa_circ_0007813 could regulate IGF2R expression via hsa-miR-361-3p sponging. The potential of hsa_circ_0007813 in regulating IGF2R expression explained its influence on cell behavior and clinical outcomes. Collectively, our data could offer new insight into the biology of circRNA in bladder cancer.
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ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-021-04053-4