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.
Highlights
Nasopharyngeal carcinoma (NPC), one of the most common malignant tumors of head and neck cancer in southern China, has distinct racial and regional characteristics [1, 2]
We found that TRIP4, clustered within the same genomic neighborhoods of KIAA0101, was identified to have the similar expression patterns in GDS2520 and The Cancer Genome Atlas (TCGA) Head-Neck Squamous Cell Carcinoma (HNSC) samples, which may be co-regulated by the same transcriptional factor ELK1
After normalization to get rid of biases in microarray data, results of heatmap and volcano plot showed that KIAA0101 was ranked top in differential gene lists (Figure 1A, 1B)
Summary
Nasopharyngeal carcinoma (NPC), one of the most common malignant tumors of head and neck cancer in southern China, has distinct racial and regional characteristics [1, 2]. It is urgent to identify new molecular basis behind the pathogenesis of NPC www.aging-us.com and explore efficient therapeutic targets for NPC patients. Increasing evidence has revealed that KIAA0101 plays a multifunctional role in biological process regulations of human cancer development such as cell proliferation [10], migration [11], DNA repair [12], cell cycle [10], and chemoresistance [13]. Neha Jain group found that miR-197-5p suppressed proliferation, invasion, migration and induced cellular senescence of HT1080 fibrosarcoma cells by targeting KIAA0101 [14]. Overexpression of KIAA0101 predicted poor prognosis and promoted the proliferation of rectal cancer [16], hepatocellular carcinoma [17], adrenal cancer [18], pancreatic cancer [9] and gastric cancer cells [19]. Whether KIAA0101 is involved in the oncogenesis of NPC and the molecular mechanisms by which KIAA0101 is regulated in NPC are unclear
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