Skip to main content
SpringerLink
Log in

Higher expression of cation transport regulator-like protein 1 (CHAC1) predicts of poor outcomes in uveal melanoma (UM) patients

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Objective

The purpose of our present study was to investigate the expression of cation transport regulator-like protein 1 (CHAC1) in uveal melanoma (UM) tissues and its function in UM progression.

Methods

The mRNA expression of CHAC1 in UM tissues and its prognostic value were investigated based on Gene Expression Omnibus database and The Cancer Genome Atlas database. SP6.5 and M23 UM cell lines with depleted CHAC1 were constructed using small interfering RNA. The viability and migration ability of SP6.5 and M23 UM cells were determined by MTT and wound healing assays, respectively. Western blot was conducted to test the influences of CHAC1 depletion on PI3K signaling pathway.

Results

Higher expression of CHAC1 was observed in the UM tissues from patients with liver metastases compared to that from patients without metastases. High CHAC1 expression was correlated with poor prognostic and was an independent predictor for UM patients. Depletion of CHAC1 remarkably inhibited the proliferation and motility of SP6.5 and M23 UM cells. Moreover, the ratios of p-AKT/AKT and p-mTOR/mTOR were reduced notably after silencing CHAC1.

Conclusions

Our results suggested that CHAC1 functioned as a facilitator in UM cell proliferation and migration and possessed the potential to be a predictor as well as a therapeutic target for UM patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Siegel R, Ma J, Zou Z, Jemal A, Ward E, Xu J, Siegael R, Desantis C, Zoy Z (2014) Cancer statistics, 2014. CA Cancer J Clin 62(1):10

    Article  Google Scholar 

  2. Jiang Z, Yu F, Li M (2018) Upregulation of BCL2 19 kD protein-interacting protein 3 (BNIP3) is predictive of unfavorable prognosis in uveal melanoma. Med Sci Monit 24:4711–4717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tarlan B, Kıratlı H (2016) Uveal melanoma: current trends in diagnosis and management. Turk J Ophthalmol 46(3):123–137

    Article  PubMed  PubMed Central  Google Scholar 

  4. Damato B (2012) Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture. Eye 26(9):1157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jager M, Brouwer N, Esmaeli B (2018) The Cancer Genome Atlas Project: an integrated molecular view of uveal melanoma. Ophthalmology 125(8):1139–1142

    Article  PubMed  Google Scholar 

  6. Spagnolo F, Caltabiano G, Queirolo P (2012) Uveal melanoma. Cancer Treat Rev 38(5):549–553

    Article  PubMed  Google Scholar 

  7. Goebel G, Berger R, Strasak AM, Egle D, Müllerholzner E, Schmidt S, Rainer J, Presul E, Parson W, Lang S (2012) Elevated mRNA expression of CHAC1 splicing variants is associated with poor outcome for breast and ovarian cancer patients. Br J Cancer 106(1):189–198

    Article  CAS  PubMed  Google Scholar 

  8. Zhang XD, Jiang CC, Wang YF, Wade M, Averykiejda K, Hersey P (2008) The unfolded protein response differentially regulates sensitivities of human melanoma cells to chemotherapeutic drugs. Cancer Res 68:715

    Article  Google Scholar 

  9. Shuda M, Kondoh N, Imazeki N, Tanaka K, Okada T, Mori K, Hada A, Arai M, Wakatsuki T, Matsubara O (2003) Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis. J Hepatol 38(5):605–614

    Article  CAS  PubMed  Google Scholar 

  10. Scriven P, Brown N, Pockley A, Wyld L (2007) The unfolded protein response and cancer: a brighter future unfolding? J Mol Med 85(4):331–341

    Article  CAS  PubMed  Google Scholar 

  11. Jahn B, Arvandi M, Rochau U, Fiegl H, Goebel G, Marth C, Siebert U (2017) Development of a novel prognostic score for breast cancer patients using mRNA expression of CHAC1. J Comp Eff Res 6(7):563–574

    Article  PubMed  Google Scholar 

  12. Chen P, Shen W, Shih C, Ho K, Cheng C, Lin C, Lee C, Liu A, Chen K (2017) The CHAC1-inhibited Notch3 pathway is involved in temozolomide-induced glioma cytotoxicity. Neuropharmacology 116:300–314

    Article  CAS  PubMed  Google Scholar 

  13. Stelzer Y, Yanuka O, Benvenisty N (2011) Global analysis of parental imprinting in human parthenogenetic induced pluripotent stem cells. Nat Struct Mol Biol 18(6):735–741

    Article  CAS  PubMed  Google Scholar 

  14. Buchholz M, Braun M, Heidenblut A, Kestler H, Klöppel G, Schmiegel W, Hahn S, Lüttges J, Gress T (2005) Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions. Oncogene 24(44):6626–6636

    Article  CAS  PubMed  Google Scholar 

  15. Zhang Y, Qiao H, Zhou Y, Hong L, Chen J (2018) Fibrinogen-like-protein 1 promotes the invasion and metastasis of gastric cancer and is associated with poor prognosis. Mol Med Rep 18(2):1465–1472

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 25(4):402–408

    Article  CAS  Google Scholar 

  17. Wang M, Li X, Zhang J, Yang Q, Chen W, Jin W, Huang YR, Yang R, Gao WQ (2017) AHNAK2 is a novel prognostic marker and oncogenic protein for clear cell renal cell carcinoma. Theranostics 7(5):1100–1113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Xu W, Yang Z, Lu N (2015) A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adhes Migr 9(4):317–324

    Article  CAS  Google Scholar 

  19. Mungrue IN, Pagnon J, Kohannim O, Gargalovic PS, Lusis AJ (2009) CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade. J Immunol 182(1):466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Scriven P, Coulson S, Haines R, Balasubramanian S, Cross S, Wyld L (2009) Activation and clinical significance of the unfolded protein response in breast cancer. Br J Cancer 101(10):1692–1698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sun Y, Atmadibrata B, Yu D, Wong M, Liu B, Ho N, Ling D, Tee AE, Wang J, Mungrue IN, Liu PY (2017) Upregulation of LYAR induces neuroblastoma cell proliferation and survival. Cell Death Differ 24(9):1645–1654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Pompura S, Dominguez-Villar M (2018) The PI3K/AKT signaling pathway in regulatory T-cell development, stability, and function. J Leukoc, Biol

    Book  Google Scholar 

  23. Porta C, Paglino C, Mosca A (2014) Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol 4(4):64

    PubMed  PubMed Central  Google Scholar 

  24. Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT (2017) The PI3K pathway in human disease. Cell 170(4):605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Li Y, Sun D, Sun W, Yin D (2019) Ras-PI3K-AKT signaling promotes the occurrence and development of uveal melanoma by downregulating H3K56ac expression. J Cell Physiol. https://doi.org/10.1002/jcp.28261

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ye M, Hu D, Tu L, Zhou X, Lu F, Wen B, Wu W, Lin Y, Zhou Z, Qu J (2008) Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells. Invest Ophthalmol Vis Sci 49(2):497–504

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Yanchen Liu and Mengyun Li are equally as first authors.

Authors and Affiliations

  1. Department of Ophthalmology, Yidu Central Hospital of Weifang, Qingzhou, 262500, People’s Republic of China

    Yanchen Liu, Mengyun Li & Danping Shi

  2. Department of Ophthalmology, The Affiliated Hospital of Weifang Medical University, Weifang, 261031, People’s Republic of China

    Yuguang Zhu

Authors
  1. Yanchen Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mengyun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danping Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuguang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuguang Zhu.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Li, M., Shi, D. et al. Higher expression of cation transport regulator-like protein 1 (CHAC1) predicts of poor outcomes in uveal melanoma (UM) patients. Int Ophthalmol 39, 2825–2832 (2019). https://doi.org/10.1007/s10792-019-01129-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-019-01129-1

Keywords

Search

Navigation