Research Paper Volume 12, Issue 7 pp 5992—6017

PCNA-associated factor KIAA0101 transcriptionally induced by ELK1 controls cell proliferation and apoptosis in nasopharyngeal carcinoma: an integrated bioinformatics and experimental study

Hu Zhao 1, 2, *, , Miaosheng Chen 3, *, , Jie Wang 1, *, , Gang Cao 4, , Wei Chen 4, , Jinke Xu 4, ,

  • 1 Fujian Provincial Key Laboratory of Transplant Biology, Department of Urology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou 350025, Fujian, P.R. China
  • 2 Office of Science Education, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou 350025, Fujian, P.R. China
  • 3 Pathology Department, Longyan First Hospital Affiliated to Fujian Medical University, Longyan 364000, Fujian, P.R. China
  • 4 Department of Oral and Maxillofacial Surgery, Medical School of Nanjing University, Nanjing 210002, Jiangsu, P.R. China
* Equal contribution

received: July 22, 2019 ; accepted: March 9, 2020 ; published: April 9, 2020 ;

https://doi.org/10.18632/aging.102991
How to Cite

Copyright © 2020 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

KIAA0101, previously identified as PCNA-associated factor, is overexpressed among almost majority of human cancers and has emerged as an important regulator of cancer progression; however, its function in human nasopharyngeal carcinoma (NPC) remain unknown. Integrated bioinformatics approaches were employed to determine the KIAA0101 expressions in the NPC samples. Lentiviral vectors carrying KIAA0101 shRNA were constructed and stable transfected cells were validated by qRT-PCR and western blot. Cellular functions were then evaluated by MTT, colony formation, Brdu staining, and flow cytometry. Mechanistic studies were systematically investigated by UCSC Genome Browser, GEO, UALCAN, QIAGEN, PROMO and JASPAR, ChIP, and the cBioPortal, et al. The results showed that KIAA0101 ranked top overexpressed gene lists in GSE6631 dataset. KIAA0101 was highly expressed in NPC tissues and cell lines. Furthermore, knockdown of KIAA0101 significantly inhibited cell proliferation and DNA replication, promoted apoptosis and cell cycle arrest in vitro. Meanwhile, the mechanistic study revealed that MAP kinase phosphorylation-dependent activation of ELK1 may enhance neighbor gene expressions of KIAA0101 and TRIP4 by binding both promotor regions in the NPC cells. Taken together, our findings indicate that overexpression of KIAA0101 activated by MAP kinase phosphorylation-dependent activation of ELK1 may play an important role in NPC progression.

Abbreviations

TCGA: The Cancer Genome Atlas; ES: Enrichment Score; NES: Normalized Enrichment Score; GSEA: Gene Set Enrichment Analysis; NPC: Nasopharyngeal Cancer; HNSC: Head-Neck Squamous Cell Carcinoma; GEO: Gene Expression Omnibus; MEM: Multi Experiment Matrix; KEGG: Kyoto Encyclopedia of Genes and Genomes; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; PCNA: Proliferating cell nuclear antigen; qRT-PCR: Quantitative real-time polymerase chain reaction; ChIP: Chromatin immunoprecipitation; 5-Bromo-2-deoxyuridine: BrdU.