KIAA1199 promotes invasion and migration in non-small-cell lung cancer (NSCLC) via PI3K-Akt mediated EMT
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KIAA1199 is often upregulated in cancer cells, including non-small-cell lung cancer (NSCLC). Although KIAA1199 is associated with aggressive tumor phenotype and poor survival in NSCLC, little is known about its functional role in NSCLC progression. Using archived clinical samples, we evaluated KIAA1199 messenger RNA (mRNA) and protein expression in NSCLC tissues and correlated with NSCLC clinicopathological characteristics as well as overall survival. Using NSCLC cell lines, KIAA1199 was either silenced using gene-specific shRNA or overexpressed to assess the impact on EMT signaling pathways. Finally, in a mouse xenograft NSCLC model, we determine the therapeutic potential of KIAA1199 repression. Our data showed that KIAA1199 was significantly upregulated in NSCLC tissues compared to adjacent normal tissues both at the mRNA (P < 0.001) and protein levels (P < 0.05). KIAA1199 overexpression is an independent prognostic marker for overall survival (HR = 1.833). In NSCLC cell lines, KIAA1199 expression directly influences the expression of EMT markers, EMT-inducing transcription factors (EMT-TFs), and EMT signaling molecules. Knocking down of KIAA1199 expression in the mouse NSCLC xenograft model significantly suppressed tumor growth and augmented the efficacy of chemotherapy (n = 5; P < 0.05). We conclude that KIAA1199 is not only a prognostic marker but a novel therapeutic target in NSCLC through regulating EMT signaling pathway.
KIAA1199 overexpression is an independent prognostic marker in NSCLC.
KIAA1199 expression directly influences the expression of EMT markers.
KIAA1199 promotes invasion and migration in NSCLC via PI3K-Akt mediated EMT.
KeywordsKIAA1199 NSCLC Metastasis
Non-small-cell lung cancer
Cell migration-inducing and hyaluronan-binding protein
Human Unidentified Gene-Encoded
Cell Bank, Type Culture Collection, Chinese Academy of Science
EMT-inducing transcription factors
Fetal bovine serum
Tumor node metastasis
Reconstituted high-density lipoprotein
We thank the members of Clinical Biobank of the Affiliated Hospital of Nantong University.
Z.T. and Y.D. performed the basic experiments and analyzed the data. Q.S. and C.Z. acquired the clinical data. X.Z. and J.H. conceived the project and designed the study. J.L. and Y.W. analyzed the results. Z.T. and M.N. wrote the manuscript.
This work was supported by Key Technology Research of Nantong-People’s Livelihood (No. MS22015114), National Natural Science Foundation of China (No. 81503143), and Six Talent Peaks Project in Jiangsu Province (No. 2015-WSW-049).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethics approval and consent to participate
All animal experiments carried out in this project were following the NIH Guidelines with the ethical approval of the Administration Committee of Experimental Animals, Jiangsu Province, China.
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