Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 8/2016

01-08-2016 | Original Article

JMJD1A promotes tumorigenesis and forms a feedback loop with EZH2/let-7c in NSCLC cells

Authors: Min Zhan, Feiqiu Wen, Lijuan Liu, Zebin Chen, Hong Wei, Honghao Zhou

Published in: Tumor Biology | Issue 8/2016

Login to get access

Abstract

Lung cancer is the most common cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) accounts for 80 to 85 % of all lung cancer. Although the standard treatment regimen has been established, long-term survival for NSCLC patients is still generally poor. The histone demethylase Jumonji domain containing 1A (JMJD1A) has been proposed as an oncogene in several types of human cancer, but its clinical significance and functional roles in NSCLC remain largely unclear. In the present study, JMJD1A was frequently upregulated in NSCLC compared with para-carcinoma tissues. JMJD1A knockdown significantly inhibited NSCLC cell growth, migration, and invasion in vitro and tumorigenesis in vivo. Further experiments demonstrated that JMJD1A knockdown could decrease the expression of EZH2, which has been shown to play a crucial role in the carcinogenesis of NSCLC and, in turn, increase the expression of anti-tumor microRNA let-7c. Also, let-7c directly targeted the 3′-untranslated regions of JMJD1A and EZH2. Taken together, JMJD1A could promote NSCLC tumorigenesis. JMJD1A/EZH2/let-7c constituted a feedback loop and might represent a promising therapeutic target for NSCLC.
Literature
1.
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.CrossRefPubMed
2.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.CrossRefPubMed
3.
Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, et al. Histone demethylation mediated by the nuclear amine oxidase homolog lsd1. Cell. 2004;119:941–53.CrossRefPubMed
4.
Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, et al. Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2006;439:811–6.CrossRefPubMed
5.
6.
Okada Y, Scott G, Ray MK, Mishina Y, Zhang Y. Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis. Nature. 2007;450:119–23.CrossRefPubMed
7.
Yamane K, Toumazou C, Tsukada Y, Erdjument-Bromage H, Tempst P, Wong J, et al. JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell. 2006;125:483–95.CrossRefPubMed
8.
Suikki HE, Kujala PM, Tammela TL, van Weerden WM, Vessella RL, Visakorpi T. Genetic alterations and changes in expression of histone demethylases in prostate cancer. Prostate. 2010;70:889–98.PubMed
9.
Guo X, Shi M, Sun L, Wang Y, Gui Y, Cai Z, et al. The expression of histone demethylase JMJD1A in renal cell carcinoma. Neoplasma. 2011;58:153–7.CrossRefPubMed
10.
Cho HS, Toyokawa G, Daigo Y, Hayami S, Masuda K, Ikawa N, et al. The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene. Int J Cancer. 2012;131:E179–189.CrossRefPubMed
11.
Yamada D, Kobayashi S, Yamamoto H, Tomimaru Y, Noda T, Uemura M, et al. Role of the hypoxia-related gene, JMJD1A, in hepatocellular carcinoma: clinical impact on recurrence after hepatic resection. Ann Surg Oncol. 2012;19 Suppl 3:S355–364.CrossRefPubMed
12.
Uemura M, Yamamoto H, Takemasa I, Mimori K, Hemmi H, Mizushima T, et al. Jumonji domain containing 1A is a novel prognostic marker for colorectal cancer: in vivo identification from hypoxic tumor cells. Clin Cancer Res Off J Am Assoc Cancer Res. 2010;16:4636–46.CrossRef
13.
Tee AE, Ling D, Nelson C, Atmadibrata B, Dinger ME, Xu N, Mizukami T, Liu PY, Liu B, Cheung B, Pasquier E, Haber M, Norris MD, Suzuki T, Marshall GM, Liu T. The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1. Oncotarget. 2014.
14.
Fan L, Peng G, Sahgal N, Fazli L, Gleave M, Zhang Y, Hussain A, Qi J. Regulation of c-Myc expression by the histone demethylase JMJD1A is essential for prostate cancer cell growth and survival. Oncogene. 2015.
15.
Hirsch FR, Varella-Garcia M, Bunn Jr PA, Di Maria MV, Veve R, Bremmes RM, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol Off J Am Soc Clin Oncol. 2003;21:3798–807.CrossRef
16.
Marshall GM, Liu PY, Gherardi S, Scarlett CJ, Bedalov A, Xu N, et al. SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability. PLoS Genet. 2011;7:e1002135.CrossRefPubMedPubMedCentral
17.
Fussbroich B, Wagener N, Macher-Goeppinger S, Benner A, Falth M, Sultmann H, et al. EZH2 depletion blocks the proliferation of colon cancer cells. PLoS One. 2011;6:e21651.CrossRefPubMedPubMedCentral
18.
Liu T, Tee AE, Porro A, Smith SA, Dwarte T, Liu PY, et al. Activation of tissue transglutaminase transcription by histone deacetylase inhibition as a therapeutic approach for Myc oncogenesis. Proc Natl Acad Sci U S A. 2007;104:18682–7.CrossRefPubMedPubMedCentral
19.
Ma X, Li C, Sun L, Huang D, Li T, He X, et al. Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1. Nat Commun. 2014;5:5212.CrossRefPubMed
20.
Steele JC, Torr EE, Noakes KL, Kalk E, Moss PA, Reynolds GM, et al. The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens. Br J Cancer. 2006;95:1202–11.CrossRefPubMedPubMedCentral
21.
Piskounova E, Polytarchou C, Thornton JE, LaPierre RJ, Pothoulakis C, Hagan JP, et al. Lin28a and lin28b inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell. 2011;147:1066–79.CrossRefPubMedPubMedCentral
22.
Hayashi Y, Tsujii M, Wang J, Kondo J, Akasaka T, Jin Y, et al. CagA mediates epigenetic regulation to attenuate let-7 expression in Helicobacter pylori-related carcinogenesis. Gut. 2013;62:1536–46.CrossRefPubMed
23.
Sun D, Layer R, Mueller AC, Cichewicz MA, Negishi M, Paschal BM, et al. Regulation of several androgen-induced genes through the repression of the miR-99a/let-7c/miR-125b-2 miRNA cluster in prostate cancer cells. Oncogene. 2014;33:1448–57.CrossRefPubMed
24.
Zhang W, Liu H, Liu W, Liu Y, Xu J. Polycomb-mediated loss of microRNA let-7c determines inflammatory macrophage polarization via PAK1-dependent NF-κB pathway. Cell Death Differ. 2015;22:287–97.CrossRefPubMed
25.
Tzatsos A, Paskaleva P, Lymperi S, Contino G, Stoykova S, Chen Z, et al. Lysine-specific demethylase 2b (KDM2B)-let-7-enhancer of zester homolog 2 (EZH2) pathway regulates cell cycle progression and senescence in primary cells. J Biol Chem. 2011;286:33061–9.CrossRefPubMedPubMedCentral
26.
Kong D, Heath E, Chen W, Cher ML, Powell I, Heilbrun L, et al. Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS One. 2012;7:e33729.CrossRefPubMedPubMedCentral
27.
Wade MA, Jones D, Wilson L, Stockley J, Coffey K, Robson CN, et al. The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer. Nucleic Acids Res. 2015;43:196–207.CrossRefPubMed
28.
Parrish JK, Sechler M, Winn RA, Jedlicka P. The histone demethylase KDM3A is a microRNA-22-regulated tumor promoter in Ewing sarcoma. Oncogene. 2015;34:257–62.CrossRefPubMed
29.
Osawa T, Tsuchida R, Muramatsu M, Shimamura T, Wang F, Suehiro J, et al. Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor-associated macrophages. Cancer Res. 2013;73:3019–28.CrossRefPubMed
30.
Krieg AJ, Rankin EB, Chan D, Razorenova O, Fernandez S, Giaccia AJ. Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. Mol Cell Biol. 2010;30:344–53.CrossRefPubMed
31.
Au SL, Wong CC, Lee JM, Fan DN, Tsang FH, Ng IO, et al. Enhancer of zeste homolog 2 epigenetically silences multiple tumor suppressor microRNAs to promote liver cancer metastasis. Hepatology. 2012;56:622–31.CrossRefPubMed
32.
Fujii S, Tokita K, Wada N, Ito K, Yamauchi C, Ito Y, et al. MEK-ERK pathway regulates EZH2 overexpression in association with aggressive breast cancer subtypes. Oncogene. 2011;30:4118–28.CrossRefPubMed
33.
34.
Behrens C, Solis LM, Lin H, Yuan P, Tang X, Kadara H, et al. Wistuba, II: EZH2 protein expression associates with the early pathogenesis, tumor progression, and prognosis of non-small cell lung carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2013;19:6556–65.CrossRef
35.
Liu L, Xu Z, Zhong L, Wang H, Jiang S, Long Q, et al. Prognostic value of EZH2 expression and activity in renal cell carcinoma: a prospective study. PLoS One. 2013;8:e81484.CrossRefPubMedPubMedCentral
36.
Knudsen ES, Dervishaj O, Kleer CG, Pajak T, Schwartz GF, Witkiewicz AK. EZH2 and aldh1 expression in ductal carcinoma in situ: complex association with recurrence and progression to invasive breast cancer. Cell Cycle. 2013;12:2042–50.CrossRefPubMedPubMedCentral
37.
Wang X, Zhao H, Lv L, Bao L, Wang X, Han S. Prognostic significance of EZH2 expression in non-small cell lung cancer: a meta-analysis. Sci Rep. 2016;6:19239.CrossRefPubMedPubMedCentral
38.
Li Z, Xu L, Tang N, Xu Y, Ye X, Shen S, et al. The polycomb group protein EZH2 inhibits lung cancer cell growth by repressing the transcription factor Nrf2. FEBS Lett. 2014;588:3000–7.CrossRefPubMed
39.
Xu C, Hou Z, Zhan P, Zhao W, Chang C, Zou J, et al. EZH2 regulates cancer cell migration through repressing TIMP-3 in non-small cell lung cancer. Med Oncol. 2013;30:713.CrossRefPubMed
40.
Sun M, Liu XH, Lu KH, Nie FQ, Xia R, Kong R, et al. EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition. Cell Death Dis. 2014;5:e1298.CrossRefPubMedPubMedCentral
41.
Nadiminty N, Tummala R, Lou W, Zhu Y, Shi XB, Zou JX, et al. MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth. PLoS One. 2012;7:e32832.CrossRefPubMedPubMedCentral
42.
Han HB, Gu J, Zuo HJ, Chen ZG, Zhao W, Li M, et al. Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer. J Pathol. 2012;226:544–55.CrossRefPubMed
43.
Zhu XM, Wu LJ, Xu J, Yang R, Wu FS. Let-7c microRNA expression and clinical significance in hepatocellular carcinoma. J Int Med Res. 2011;39:2323–9.CrossRefPubMed
44.
Motoyama K, Inoue H, Nakamura Y, Uetake H, Sugihara K, Mori M. Clinical significance of high mobility group a2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14:2334–40.CrossRef
45.
Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64:3753–6.CrossRefPubMed
46.
Navarro A, Marrades RM, Vinolas N, Quera A, Agusti C, Huerta A, et al. MicroRNAs expressed during lung cancer development are expressed in human pseudoglandular lung embryogenesis. Oncology. 2009;76:162–9.CrossRefPubMed
47.
Nagayama K, Kohno T, Sato M, Arai Y, Minna JD, Yokota J. Homozygous deletion scanning of the lung cancer genome at a 100-kb resolution. Genes Chromosomes Cancer. 2007;46:1000–10.CrossRefPubMed
48.
Wang PY, Sun YX, Zhang S, Pang M, Zhang HH, Gao SY, et al. Let-7c inhibits A549 cell proliferation through oncogenic TRIB2 related factors. FEBS Lett. 2013;587:2675–81.CrossRefPubMed
49.
Zhan M, Qu Q, Wang G, Liu YZ, Tan SL, Lou XY, et al. Let-7c inhibits NSCLC cell proliferation by targeting HOXA1. Asian Pac J Cancer Prev. 2013;14:387–92.CrossRefPubMed
50.
Zhao B, Han H, Chen J, Zhang Z, Li S, Fang F, et al. MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3. Cancer Lett. 2014;342:43–51.CrossRefPubMed
51.
Wang H, Zhao Q, Deng K, Guo X, Xia J. Lin28: an emerging important oncogene connecting several aspects of cancer. Tumour Biol J Int Soc Oncodev Biol Med. 2016.
52.
Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell. 2012;148:259–72.CrossRefPubMed
53.
Zhou J, Ng SB, Chng WJ. Lin28/lin28b: an emerging oncogenic driver in cancer stem cells. Int J Biochem Cell Biol. 2013;45:973–8.CrossRefPubMed
Metadata
Title
JMJD1A promotes tumorigenesis and forms a feedback loop with EZH2/let-7c in NSCLC cells
Authors
Min Zhan
Feiqiu Wen
Lijuan Liu
Zebin Chen
Hong Wei
Honghao Zhou
Publication date
01-08-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 8/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-4999-9

Other articles of this Issue 8/2016

Tumor Biology 8/2016 Go to the issue

Original Article

Combination of 5-fluorouracil and 2-morphilino-8-phenyl-4H-chromen-4-one may inhibit liver cancer stem cell activity

Original Article

RETRACTED ARTICLE: Evaluation of mRNA expression levels of IL-17A and IL-10 cytokines in cervical cancer

Original Article

C6 ceramide sensitizes the anti-hepatocellular carcinoma (HCC) activity by AZD-8055, a novel mTORC1/2 dual inhibitor

Original Article

MGMT in colorectal cancer: a promising component of personalized treatment

Original Article

Low expression of PIDD is associated with cell proliferation and apoptosis in hepatocellular carcinoma

Original Article

ΔNp63 regulates cell proliferation, differentiation, adhesion, and migration in the BL2 subtype of basal-like breast cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits