ZWINT is the next potential target for lung cancer therapy
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We aimed to analyze the expression of ZWINT, NUSAP1, DLGAP5, and PRC1 in tumor tissues and adjacent tissues with public data.
The expression patterns of four genes were detected in cancer tissues and adjacent tissues by qRT-PCR. The overall survival analysis was used to explore these genes in lung adenocarcinoma and squamous cell carcinoma patients. Knockdown assays were used to select the most suitable gene among these four genes. Cell function assays with the knockdown gene were conducted in A549 and NCL H226 cells. The role of the knockdown gene in lung cancer was dissected in a mice tumor model. Transcriptome sequencing analyses with the knockdown gene were analyzed.
Overexpression of these genes was significantly detected in cancer tissues (P < 0.01). Overall survival revealed that high expression of these genes is closely related with poor prognosis of lung adenocarcinoma patients (P < 0.05). Knockdown of ZWINT reduced proliferation in NCI H226 and A549 cells (P < 0.05). Knockdown also inhibited cell migration, invasion, apoptosis, and colony formation (P < 0.05). ZWINT knockdown reduced tumor volume (P < 0.05). Transcriptome sequencing of ZWINT knockdown-treated A549 and NCI H226 cells indicated that 100 and 426 differentially expressed genes were obtained, respectively. Gene ontology analysis suggested that binding, biological regulation, and multicellular organismal processes were the most enriched. KEGG analysis revealed that TNF, P53, and PI3K signal networks would be the most potential ZWINT-related pathways and were identified by Western blot analysis.
ZWINT may be a novel target for lung cancer therapy.
KeywordsLung cancer ZWINT Differentially expressed genes Gene ontology KEGG
FP, QL, and S-QN: bioinformatics analysis and writing of the manuscript. G-PS and YL: the discussion. MC and YB: discussion and comments on an earlier version of the manuscript. All authors read and approved the final manuscript.
This work was supported in part by the National Natural Science Foundation of China (no. 81602661), the Natural Science Foundation of Guangdong Province, China (no. 2016A030310164). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Compliance with ethical standards
Conflict of interest
The author(s) declare that they have no competing interests.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards The Research Ethics Committee of Sun Yat-Sen University approved the collection of tissue samples for research.
- Cooper WA, Lam DC, O’Toole SA, Minna JD (2013) Molecular biology of lung cancer. J Thorac Dis 5(Suppl 5):S479–S490 https://doi.org/10.3978/j.issn.2072-1439.2013.08.03 CrossRefPubMedPubMedCentralGoogle Scholar
- Hata A et al (2013) Rebiopsy of non-small cell lung cancer patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor: comparison between T790M mutation-positive and mutation-negative populations. Cancer 119:4325–4332. https://doi.org/10.1002/cncr.28364 CrossRefPubMedGoogle Scholar
- Nakamura T et al (2004) Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection. Oncogene 23:2385–2400. https://doi.org/10.1038/sj.onc.1207392 CrossRefPubMedGoogle Scholar
- Remon J, Moran T, Majem M, Reguart N, Dalmau E, Marquez-Medina D, Lianes P (2014) Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: a new era begins. Cancer Treat Rev 40:93–101. https://doi.org/10.1016/j.ctrv.2013.06.002 CrossRefPubMedGoogle Scholar