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posted on 2023-03-31, 02:04 authored by Mantang Qiu, Wenjia Xia, Rui Chen, Siwei Wang, Youtao Xu, Zhifei Ma, Weizhang Xu, Erbao Zhang, Jie Wang, Tian Fang, Jingwen Hu, Gaochao Dong, Rong Yin, Jun Wang, Lin Xu Biological functions of miR-545 and miR-589. A: Schematic diagram showing the putative binding sites of the miRNAs associated with circPRKCI. B, C and E: miR-545 and miR-589 inhibit the proliferation of SPC-A1 cells, as shown by CCK-8, EDU, and colony formation assays. D: miR-545 and miR-589 induce G1 phase cell cycle arrest. ** P <0.01, N.S: not significant; NC: negative control
Funding
National Natural Science Foundation of China
Innovation Capability Development Project of Jiangsu Province
Department of Surgery and the Cancer Research Center
History
ARTICLE ABSTRACT
Somatic copy number variations (CNV) may drive cancer progression through both coding and noncoding transcripts. However, noncoding transcripts resulting from CNV are largely unknown, especially for circular RNAs. By integrating bioinformatics analyses of alerted circRNAs and focal CNV in lung adenocarcinoma, we identify a proto-oncogenic circular RNA (circPRKCI) from the 3q26.2 amplicon, one of the most frequent genomic aberrations in multiple cancers. circPRKCI was overexpressed in lung adenocarcinoma tissues, in part due to amplification of the 3q26.2 locus, and promoted proliferation and tumorigenesis of lung adenocarcinoma. circPRKCI functioned as a sponge for both miR-545 and miR-589 and abrogated their suppression of the protumorigenic transcription factor E2F7. Intratumor injection of cholesterol-conjugated siRNA specifically targeting circPRKCI inhibited tumor growth in a patient-derived lung adenocarcinoma xenograft model. In summary, circPRKCI is crucial for tumorigenesis and may serve as a potential therapeutic target in patients with lung adenocarcinoma.Significance: These findings reveal high expression of the circular RNA circPRKCI drives lung adenocarcinoma tumorigenesis. Cancer Res; 78(11); 2839–51. ©2018 AACR.
