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STIL is upregulated in nasopharyngeal carcinoma tissues and promotes nasopharyngeal carcinoma proliferation, migration and invasion

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Ying Ouyang, Ya-Bin Jin, Xiang-Ping Chen, Guo-Yi Zhang, Shao-Long Mao,  Fei Ling,  Wei Luo

Abstract:

Nasopharyngeal carcinoma (NPC) is the most common primary malignancy that originates from the nasopharynx. Some regulatory networks involved in nasopharyngeal carcinoma have been reported, but the relevant genes have not been fully identified. We have used mRNA microarray to identify differential expression genes between NPC tissues and adjacent normal tissues. Then high-content shRNA screening was carried out to screen the genes that may control proliferation in nasopharyngeal carcinoma. Cell proliferation was monitored by MTT assays and Celigo image cytometry in vitro and by subcutaneous transplantation model in vivo. Flow cytometric analysis was carried out to detect the distribution of cell cycle stages and apoptosis. Transwell assay was performed to measure the migratory and invasive capacities of NPC cells. We identified 20 genes that potentially play an important role in the proliferation of nasopharyngeal carcinoma by mRNA microarray and functional analysis. The result of high-content shRNA screening indicated that STIL had the greatest effect on reducing the proliferation rate of NPC cells. The analysis of The Cancer Genome Atlas (TCGA) data showed that STIL was upregulated in several human cancer tissues, and higher STIL expression level was correlated with shorter survival time. STIL knockdown also inhibited NPC cell migration and invasion, promoted G1/S phase transition and apoptosis. Three genes including ITGA2, SMAD2, JAK1, associated with molecular mechanisms of cancer were influenced by downregulating STIL. Our study confirmed STIL as a key regulator that promotes the proliferation of NPC, providing insight into the molecular mechanisms of nasopharyngeal carcinoma and suggesting a novel therapeutic strategy.

Received date: 03/06/2019

Accepted date: 05/22/2019

Ahead of print publish date: 10/09/2019

Issue: 1/2020

Volume: 67

Pages: 37 — 45

Keywords: STIL, nasopharyngeal carcinoma, cell proliferation, High-content shRNA screening, mRNA microarray

Supplementary files:
Suppl file 1 - TE.pdf
Suppl file 2. Raw Data Files - TE.zip
Suppl file 3. Raw Data Files - TE.zip

DOI: 10.4149/neo_2019_190306N192

Pubmed

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