Tumor Biology

, Volume 37, Issue 1, pp 1113–1120 | Cite as

LRRC3B is downregulated in non-small-cell lung cancer and inhibits cancer cell proliferation and invasion

  • Liang Kan
  • Hui Li
  • Yi Zhang
  • Jiahe Wang
  • Huiyan Niu
  • Hongfang Jiang
  • Meng Zhang
  • Xue Bai
  • Ping He
Original Article


LRRC3B has emerged as a tumor suppressor in several human cancers. However, its expression pattern and biological roles in human non-small-cell lung cancer (NSCLC) have not been explored. In the present study, we investigated clinical significance of LRRC3B in 101 NSCLC specimens. We found that LRRC3B expression was downregulated in NSCLC tissues compared with normal bronchial epithelium and that its downregulation significantly correlated with tumor–node–metastasis (TNM) stage (p < 0.0001), nodal metastasis (p < 0.0001), and poor patient prognosis (p = 0.0016, log-rank test). We also checked LRRC3B levels in several lung cancer cell lines and found that its expression was downregulated in four of nine lung cancer cell lines compared with normal human bronchial epithelial (NHBE) cell line. We further explored the biological role of LRRC3B. LRRC3B plasmid transfection in H460 and A549 cell lines inhibited proliferation, colony formation ability, and invading ability. Furthermore, we identified that LRRC3B could inhibit cell cycle progression with downregulation of cyclin D1 and decreased MMP9 expression. In addition, LRRC3B depletion in HBE cells promoted proliferation and invasion. In conclusion, our data suggested that LRRC3B may serve as an important tumor suppressor in NSCLC.


LRRC3B Non-small-cell lung cancer Proliferation Invasion 



The study was supported by Outstanding Scientific Fund of Shengjing Hospital (No. 201205).

Conflicts of interest


Supplementary material

13277_2015_3833_Fig5_ESM.gif (63 kb)
Supplementary Figure 1

LRRC3B depletion promotes growth, invasion, cyclin D1 and MMP9. A. Western blot analysis showed that siRNA markedly decreases its levels in HBE cells compared with control. B. MTT assay showed that LRRC3B depletion increased cell growth rate. C. Colony formation assay showed that LRRC3B depletion increased colony number. D. Matrigel invasion assay showed that LRRC3B depletion facilitated HBE cell invasion. E. Western blot analysis showed that LRRC3B depletion slightly upregulated cyclin D1 and MMP9. (GIF 62 kb)

13277_2015_3833_MOESM1_ESM.tif (688 kb)
High resolution image (TIFF 687 kb)


  1. 1.
    Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57(1):43–66.CrossRefPubMedGoogle Scholar
  2. 2.
    Minna JD, Roth JA, Gazdar AF. Focus on lung cancer. Cancer Cell. 2002;1(1):49–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Dong QZ, Wang Y, Dong XJ, Li ZX, Tang ZP, Cui QZ, et al. CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis. Ann Surg Oncol.Google Scholar
  5. 5.
    Dong QZ, Zhao Y, Liu Y, Wang Y, Zhang PX, Jiang GY, et al. Overexpression of SCC-S2 correlates with lymph node metastasis and poor prognosis in patients with non-small-cell lung cancer. Cancer Sci. 101(6):1562–9.Google Scholar
  6. 6.
    Fidler IJ, Kripke ML. Genomic analysis of primary tumors does not address the prevalence of metastatic cells in the population. Nat Genet. 2003;34(1):23. author reply 25.CrossRefPubMedGoogle Scholar
  7. 7.
    van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.CrossRefGoogle Scholar
  8. 8.
    Kobe B, Deisenhofer J. A structural basis of the interactions between leucine-rich repeats and protein ligands. Nature. 1995;374(6518):183–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Kajava AV, Kobe B. Assessment of the ability to model proteins with leucine-rich repeats in light of the latest structural information. Protein Sci. 2002;11(5):1082–90.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kobe B, Kajava AV. The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol. 2001;11(6):725–32.CrossRefPubMedGoogle Scholar
  11. 11.
    Kajava AV. Structural diversity of leucine-rich repeat proteins. J Mol Biol. 1998;277(3):519–27.CrossRefPubMedGoogle Scholar
  12. 12.
    Bianchini M, Levy E, Zucchini C, Pinski V, Macagno C, De Sanctis P, et al. Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa. Int J Oncol. 2006;29(1):83–94.PubMedGoogle Scholar
  13. 13.
    Kim M, Kim JH, Jang HR, Kim HM, Lee CW, Noh SM, et al. LRRC3B, encoding a leucine-rich repeat-containing protein, is a putative tumor suppressor gene in gastric cancer. Cancer Res. 2008;68(17):7147–55.CrossRefPubMedGoogle Scholar
  14. 14.
    Tian XQ, Zhang Y, Sun D, Zhao S, Xiong H, Fang J. Epigenetic silencing of LRRC3B in colorectal cancer. Scand J Gastroenterol. 2009;44(1):79–84.CrossRefPubMedGoogle Scholar
  15. 15.
    Kondratov AG, Stoliar LA, Kvasha SM, Gordiyuk VV, Zgonnyk YM, Gerashchenko AV, et al. Methylation pattern of the putative tumor-suppressor gene LRRC3B promoter in clear cell renal cell carcinomas. Mol Med Rep. 2012;5(2):509–12.PubMedGoogle Scholar
  16. 16.
    Haraldson K, Kashuba VI, Dmitriev AA, Senchenko VN, Kudryavtseva AV, Pavlova TV, et al. LRRC3B gene is frequently epigenetically inactivated in several epithelial malignancies and inhibits cell growth and replication. Biochimie. 2012;94(5):1151–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Liu J, Liao Q, Zhang Y, Sun S, Zhong C, Liu X. Cyclin D1 G870A polymorphism and lung cancer risk: a meta-analysis. Tumour Biol. 33(5):1467–76.Google Scholar
  18. 18.
    Liu Y, Wang L, Lin XY, Wang J, Yu JH, Miao Y, et al. The transcription factor DEC1 (BHLHE40/STRA13/SHARP-2) is negatively associated with TNM stage in non-small-cell lung cancer and inhibits the proliferation through cyclin D1 in A549 and BE1 cells. Tumour Biol. 34(3):1641–50.Google Scholar
  19. 19.
    Dong QZ, Wang Y, Tang ZP, Fu L, Li QC, Wang ED, et al. Derlin-1 is overexpressed in non-small cell lung cancer and promotes cancer cell invasion via EGFR-ERK-mediated up-regulation of MMP-2 and MMP-9. Am J Pathol. 2013;182(3):954–64.CrossRefPubMedGoogle Scholar
  20. 20.
    Jian H, Zhao Y, Liu B, Lu S. SEMA4b inhibits MMP9 to prevent metastasis of non-small cell lung cancer. Tumour Biol. 2014;35(11):11051–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Song H, Tian Z, Qin Y, Yao G, Fu S, Geng J. Astrocyte elevated gene-1 activates MMP9 to increase invasiveness of colorectal cancer. Tumour Biol. 2014;35(7):6679–85.CrossRefPubMedGoogle Scholar
  22. 22.
    Feng X, Miao G, Han Y, Xu Y. CARMA3 is overexpressed in human glioma and promotes cell invasion through MMP9 regulation in A172 cell line. Tumour Biol. 2014;35(1):149–54.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Liang Kan
    • 1
  • Hui Li
    • 1
  • Yi Zhang
    • 1
  • Jiahe Wang
    • 1
  • Huiyan Niu
    • 1
  • Hongfang Jiang
    • 1
  • Meng Zhang
    • 1
  • Xue Bai
    • 1
  • Ping He
    • 1
    • 2
  1. 1.Department of GeriatricsShengjing Hospital of China Medical UniversityShenyangChina
  2. 2.Department of GeriatricsShengjing HospitalShenyangChina

Personalised recommendations