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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 …