Pecanex functions as a competitive endogenous RNA of S-phase kinase associated protein 2 in lung cancer

• Published in: Cancer letters 2017-10, Vol.406, p.36-46
• Main Authors: Li, Jingqiu, Tian, Haihua, Pan, Jinchang, Jiang, Nan, Yang, Jie, Zhou, Chengwei, Xu, Dazhi, Meng, Xiaodan, Gong, Zhaohui
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; AKT protein; Apoptosis; Breast cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Cycle; Cell growth; Cell proliferation; ceRNA; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Infrared imaging systems; Insects; Kinases; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; MicroRNAs; MicroRNAs - genetics; miRNA; mRNA; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Non-small cell lung carcinoma; PCNX-3′UTR; Phosphorylation; Plasmids; Proteins; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; RNA, Messenger - genetics; S-Phase Kinase-Associated Proteins - genetics; S-Phase Kinase-Associated Proteins - metabolism; Skp2-3′UTR; Stem cells; Tissues; Tumor Cells, Cultured; Tumorigenesis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.07.030

Investigating the RNA-RNA interactions involving in the initiation and progression of non-small cell lung cancer (NSCLC) may provide promising diagnostic and targeted therapeutic strategies. Here, we showed that pecanex (PCNX) positively regulates the mRNA and protein expressions of S-phase kinase associated protein 2 (Skp2) in miRNA- and 3′ UTR-dependent manners. And miR-26, miR-182, miR-340 and miR-506 were verified as the common miRNAs shared by Skp2 and PCNX. Intriguingly, we initially uncovered that PCNX-3′ UTR promotes cell growth, proliferation and cell cycle progression, and suppresses apoptosis of lung cancer cells, which is consistent with the oncogenic activity of Skp2-3′ UTR. Consequently, PCNX was identified as a competitive endogenous RNA (ceRNA) of Skp2. Moreover, knockdown of PCNX inhibits EGF-induced Akt phosphorylation, which can be reversed by the silencing of Dicer. Finally, we further discovered that Skp2 and PCNX are coordinately upregulated in lung cancer tissues compared with the adjacent non-tumor tissues. Our study establishes for the first time the oncogenic property of PCNX-3′ UTR and Skp2-3′ UTR, and the PCNX-miRNA-Skp2 regulatory pattern, which may offer a molecular basis for the diagnosis and targeted therapy in NSCLC. •PCNX competes with Skp2 in 3′ UTR- and miRNA-dependent manners.•PCNX and Skp2 share miR-26, miR-182, miR-340 and miR-506.•PCNX positively regulates Skp2.•PCNX-3′ UTR and Skp2-3′ UTR have a similar oncogenic property.•Skp2 and PCNX are coordinately upregulated in the tissues of lung cancer.