FeiFei Ma1, Cheng Zhi2, Minling Wang3, Tao Li4, Shahzad Akbar Khan5, Zhaoen Ma6, Zhiliang Jing7, Chen Bo3, Qiang Zhou3, Shaomei Xia3, Shiwen Huang3, Sicong Huang3, Zhiquan Zhang3, Hongyun Jia3, Xiaogang Cui8, Mingze Yao9, Tianxing Ji10. 1. Department of Clinical Obstetrics, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China. 2. Department of Clinical Pathology, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China. 3. Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China. 4. Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, No. 1 Xincheng Road, Songshan Lake High-tech Industrial Development Zone, Dongguan, Guangdong 523808, China. Electronic address: taoliby@hotmail.com. 5. Laboratory of Pathology, Department of Pathobiology, University of the Poonch, Rawalakot 12350, Pakistan. 6. Department of Clinical Earnosethroat, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China. 7. Department of Clinical Pathology, The Affiliated Hospital of Guangdong Medical University, No. 57 Renmin Road, Zhanjiang, Guangdong 524001, China. 8. Institutes of Biomedical Sciences, Shanxi University, No. 92 Wucheng Road, Taiyuan, Shanxi 030006, China. 9. Institutes of Biomedical Sciences, Shanxi University, No. 92 Wucheng Road, Taiyuan, Shanxi 030006, China. Electronic address: Yaomz@sxu.edu.cn. 10. Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang Road, Guangzhou, Guangdong 510260, China. Electronic address: jitianxing7021@163.com.
Abstract
BACKGROUND: Nasopharyngeal carcinoma (NPC) is common in Southern China. The molecular mechanism underlying NPC genesis and progression has been comprehensively investigated, but the key gene (s) or pathway (s) pertaining to NPC are unidentified. METHODS: We explored some key genes and pathways involved in NPC through using meta-analysis of deposited expression of microarray data of NPC. The expression of proliferating cell nuclear antigen clamp associated factor (PCLAF) was determined by real-time PCR and western blots. CCK-8 assay, colony formation assay, transwell migration assay, cell wound healing assay, cell cycle analysis and cell apoptosis were carried out to assess biological behaviors caused by downregulation and overexpression of PCLAF in vitro. CHIP was utilized to determine the direct upstream regulatory transcription factors of PCLAF. RESULTS: PCLAF was the key gene of NPC, which was significantly up-regulated in NPC cell line compared to the normal nasopharyngeal cell line. Additionally, in vitro assay has demonstrated the down-regulation and overexpression of PCLAF, resulted in significantly suppressed and enhanced NPC proliferation, metastasis and invasion respectively. Furthermore, the up-regulation of PCLAF in NPC is induced by direct binding of dysregulated NF-κB p50/RelB complex to the promoter of PCLAF. CONCLUSION: Our results offer a strategy for re-using the deposited data to find the key genes and pathways involved in pathogenesis of cancer. Our study has provided evidence of supporting the role of PCLAF in NPC genesis and progression.
BACKGROUND: Nasopharyngeal carcinoma (NPC) is common in Southern China. The molecular mechanism underlying NPC genesis and progression has been comprehensively investigated, but the key gene (s) or pathway (s) pertaining to NPC are unidentified. METHODS: We explored some key genes and pathways involved in NPC through using meta-analysis of deposited expression of microarray data of NPC. The expression of proliferating cell nuclear antigen clamp associated factor (PCLAF) was determined by real-time PCR and western blots. CCK-8 assay, colony formation assay, transwell migration assay, cell wound healing assay, cell cycle analysis and cell apoptosis were carried out to assess biological behaviors caused by downregulation and overexpression of PCLAF in vitro. CHIP was utilized to determine the direct upstream regulatory transcription factors of PCLAF. RESULTS: PCLAF was the key gene of NPC, which was significantly up-regulated in NPC cell line compared to the normal nasopharyngeal cell line. Additionally, in vitro assay has demonstrated the down-regulation and overexpression of PCLAF, resulted in significantly suppressed and enhanced NPC proliferation, metastasis and invasion respectively. Furthermore, the up-regulation of PCLAF in NPC is induced by direct binding of dysregulated NF-κB p50/RelB complex to the promoter of PCLAF. CONCLUSION: Our results offer a strategy for re-using the deposited data to find the key genes and pathways involved in pathogenesis of cancer. Our study has provided evidence of supporting the role of PCLAF in NPC genesis and progression.