title: piR-651 promotes tumor formation in non-small cell lung carcinoma through the upregulation of cyclin D1 and CDK4.
abstract: Piwi-interacting RNAs (piRNAs or piRs) are a novel class of non-coding RNAs that participate in germline development by silencing transposable elements and regulating gene expression. To date, the association between piRNAs and non‑small cell lung carcinoma (NSCLC) has not yet been elucidated. In the present study, we have demonstrated that a significant increase in piR-651 expression occurs in NSCLC. Furthermore, the abnormal expression of piR-651 was associated with cancer progression in the patients with NSCLC. The upregulation of piR-651 in A549 cells caused a significant increase in cell viability and metastasis. The percentage of arrested cells in the G0/G1 phase was lower after piR-651 overexpression compared with the controls. We also examined the expression of oncogenes and cancer suppressor genes following piR-651 overexpression in NSCLC cells. Only the expression levels of cyclin D1 and CDK4 significantly correlated with piR-651 expression both in vivo and in vitro. Furthermore, by injecting nude mice with A549 cells transfected with piR-651 plasmids to establish a xenograft model, we demonstrated that there was a correlation between piR-651 overexpression and tumor growth, which was mediated by cyclin D1 and CDK4. These findings strongly support the notion that piR-651 induces NSCLC progression through the cyclin D1 and CDK4 pathway and it may have applications as a potential diagnostic indicator and therapeutic target in the management of NSCLC.
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yingquan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Shengyu
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics; D015854:Up-Regulation
chemical_list: D034741:RNA, Small Interfering; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4