RP11-480I12.5-004 Promotes Growth and Tumorigenesis of Breast Cancer by Relieving Mir-29C-3p-mediated AKT3 and CDK6 Degradation

Pseudogenes have been reported to exert oncogenic or tumor suppressive functions in cancer. However, the expression, role, and mechanism of pseudogene-derived RNAs in breast cancer remain unclear. The RNA levels and prognostic values of pseudogenes in breast cancer were determined. The levels of RP11480I12.5 in cell lines and clinical samples were validated by quantitative real-time PCR. In vitro effects of RP11-480I12.5 on cell growth were measured by cell counting kit-8 (CCK-8) assay, colony formation assay, cell counting assay, and flow cytometry analysis. Xenograft model was established to detect its in vivo effect. The potential mechanism of RP11-480I12.5 was also studied by a combination of bioinformatic analysis and experimental confirmation. Finally, the possible functional parental genes of RP11-480I12.5 in breast cancer were explored. After a series of bioinformatic analyses, RP11-480I12.5 was selected as the most potential pseudogene in breast cancer. RP11-480I12.5 expression was significantly upregulated in breast cancer cell lines and clinical breast cancer tissues. Knockdown of RP11-480I12.5 markedly suppressed cell proliferation and colony formation, induced cell apoptosis of breast cancer in vitro, and inhibited tumor growth in vivo. Four transcripts of RP11-480I12.5 (001/002/003/004) were identified. Only over expression of RP11-480I12.5-004 significantly enhanced cell growth of breast cancer both in vitro and in vivo. RP11480I12.5-004 mainly located in cytoplasm and increased AKT3 and CDK6 mRNA expression, at least in part, by competitively binding to miR-29c-3p. Six parental genes of RP11-480I12.5 were found, among which TUBA1B and TUBA1C were statistically linked to RP11-480I12.5 expression, possessed prognostic values, and were upregulated in breast cancer. Our findings suggested that pseudogene-derived long non-coding RNA (lncRNA) RP11-480I12.5-004 promoted growth and tumorigenesis of breast cancer via increasing AKT3 and CDK6 expression by competitively binding to miR-29c-3p.