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Journal of Molecular Medicine

, Volume 97, Issue 1, pp 127–140 | Cite as

KIAA1199 promotes invasion and migration in non-small-cell lung cancer (NSCLC) via PI3K-Akt mediated EMT

  • Zhiyuan Tang
  • Yang Ding
  • Qin Shen
  • Caixin Zhang
  • Jun Li
  • Mohammed Nazar
  • Yan Wang
  • Xiaoyu ZhouEmail author
  • Jianfei HuangEmail author
Original Article
  • 156 Downloads

Abstract

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.

Key messages

  • 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.

Keywords

KIAA1199 NSCLC Metastasis 

Abbreviations

NSCLC

Non-small-cell lung cancer

CEMIP

Cell migration-inducing and hyaluronan-binding protein

HUGE

Human Unidentified Gene-Encoded

CBTCCCAS

Cell Bank, Type Culture Collection, Chinese Academy of Science

EMT

Epithelial-mesenchymal transition

EMT-TFs

EMT-inducing transcription factors

OS

Overall survival

OE

Overexpressed

SD

Standard deviation

FBS

Fetal bovine serum

IHC

Immunohistochemical

TMA

Tissue microarray

ECL

Enhanced chemiluminescence

SD

Standard deviation

TNM

Tumor node metastasis

HR

Hazard ratio

CI

Confidence interval

HDL

High-density lipoprotein

rHDL

Reconstituted high-density lipoprotein

Notes

Acknowledgments

We thank the members of Clinical Biobank of the Affiliated Hospital of Nantong University.

Authors’ contributions

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.

Funding information

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.

Supplementary material

109_2018_1721_Fig6_ESM.png (1.2 mb)
Supplementary Fig. 1

Schematic illustration of rHDL/Sh-KIAA1199 nanoparticles. a. sh-KIAA1199 was encapsulated with cationic lipid DOTAP. The complexes were loaded into rHDL to construct the gene-loaded nanoparticles by thin-film dispersion method; b, c. Graphical representation of the particle size and zeta potential of polyplexes. (PNG 1226 kb)

109_2018_1721_MOESM1_ESM.tif (2.1 mb)
High Resolution Image (TIF 2197 kb)
109_2018_1721_Fig7_ESM.png (1.8 mb)
Supplementary Fig. 2

KIAA1199 regulates migration in NSCLC cell lines. a and b. Silencing KIAA1199 by shRNA-3 reduced cell migration by Transwell assay in A549 and H1299 cell lines respectively; c and d. Overexpression of KIAA1199 increased cell migration by Transwell assay in H1975 and H1650 cell line respectively; e, f, g and h. Cell invasion assay by silencing KIAA1199 with shRNA-1 in A549 and H1299 cell lines. Data are presented as means ± SD; n = 5–8/group. * P < 0.05, ** P < 0.01, versus Control. (PNG 1834 kb)

109_2018_1721_MOESM2_ESM.tif (3.9 mb)
High Resolution Image (TIF 4023 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Zhiyuan Tang
    • 1
    • 2
  • Yang Ding
    • 3
  • Qin Shen
    • 2
  • Caixin Zhang
    • 2
  • Jun Li
    • 2
  • Mohammed Nazar
    • 2
  • Yan Wang
    • 4
  • Xiaoyu Zhou
    • 2
    Email author
  • Jianfei Huang
    • 1
    • 5
    Email author
  1. 1.Department of Clinical BiobankNantong University Affiliated HospitalNantongChina
  2. 2.Department of Respiratory MedicineAffiliated Hospital of Nantong UniversityNantongChina
  3. 3.State Key Laboratory of Natural Medicines, Department of PharmaceuticsChina Pharmaceutical UniversityNanjingChina
  4. 4.Department of Emergency MedicineAffiliated Hospital of Nantong UniversityNantongChina
  5. 5.Department of PathologyNantong University Affiliated HospitalNantongChina

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