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Critical appraisal of epigenetic regulation of galectins in cancer

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Abstract

Galectins are defined as the glycan-binding protein containing either one or two carbohydrate-binding domains and participate in various biological functions such as developmental processes, vascularisation programs, cell migration, and immune-regulation and apoptosis. Galectins are also linked to many diseases, including cancer. They are widely spread in extracellular and intracellular spaces, and their altered expression in cancer leads to tumor progression, metastasis, angiogenesis and stemness through different signalling pathways. Promoter methylation, microRNA, and histone modification constitute the epigenetic changes that regulate galectin activity in cancer. Our review discusses the concept of epigenetics in cancer and how the aforementioned factors i.e., promoter methylation, histone modification, change in miRNAs expression affect the glycomic changes in malignancies.

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Abbreviations

5mC:

5-Methylcytosine

ALL:

Lymphoblastic leukemia

CC:

Cervical cancer

CGI:

CpG islands

CRC:

Colorectal cancer

CRD:

Carbohydrate-recognition-binding domain

CpG:

Cytosine-phosphate-Guanine

DNMT:

DNA methyltransferases

FGFR:

Fibroblast growth factor receptor

GC:

Gastric cancer

Gal:

Galectin

H:

Histone

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylases

HaCaT:

Human keratinocyte cell line

K:

Lysine

LC:

Liver cancer

LNCaP:

Malignant prostate epithelial cells

LacNAc:

Lactose-Nacetyl

MUC:

Mucin

NSCLC:

Non-small-cell lung carcinoma

OC:

Ovarian cancer

PC:

Prostate cancer

PTM:

Posttranslational modifications

RACK1:

Receptor for Activated C-kinase 1

SAM:

S-Adenyl methionine

TC:

Thyroid cancer

TR:

Tandem repeat

TS:

Tumor suppressor

UTR:

Untranslated region

miRNA:

MicroRNA

References

  1. Cooper D (2002) Galectinomics: finding themes in complexity. Biochim Biophys Acta BBA Gen Subj 1572(2–3):209–231. https://doi.org/10.1016/S0304-4165(02)00310-0

    Article  CAS  Google Scholar 

  2. Wan L, Yang R-Y, Liu F-T (2018) Galectin-12 in cellular differentiation, apoptosis and polarization. Int J Mol Sci 19(1):176. https://doi.org/10.3390/ijms19010176

    Article  CAS  PubMed Central  Google Scholar 

  3. Liu F-T, Rabinovich GA (2010) Galectins: regulators of acute and chronic inflammation: galectins and inflammation. Ann N Y Acad Sci 1183(1):158–182. https://doi.org/10.1111/j.1749-6632.2009.05131.x

    Article  CAS  PubMed  Google Scholar 

  4. Vasta GR (2009) Roles of galectins in infection. Nat Rev Microbiol 7(6):424–438. https://doi.org/10.1038/nrmicro2146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Thijssen VL, Heusschen R, Caers J et al (2015) Galectin expression in cancer diagnosis and prognosis: a systematic review. Biochim Biophys Acta BBA Rev Cancer 2:235–247. https://doi.org/10.1016/j.bbcan.2015.03.003

    Article  CAS  Google Scholar 

  6. Vasta GR (2012) Galectins as pattern recognition receptors: structure, function, and evolution. In: Lambris JD, Hajishengallis G (eds) Current topics in innate immunity II. Springer, New York, pp 21–36

    Chapter  Google Scholar 

  7. Bianchet MA, Ahmed H, Vasta GR et al (2000) Soluble beta-galactosyl-binding lectin (galectin) from toad ovary: crystallographic studies of two protein-sugar complexes. Proteins 40(3):378–88. https://doi.org/10.1002/1097-0134(20000815)40:3<378::aid-prot40>3.0.co;2-7

    Article  CAS  PubMed  Google Scholar 

  8. Egger G, Liang G, Aparicio A et al (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429(6990):457–463. https://doi.org/10.1038/nature02625

    Article  CAS  PubMed  Google Scholar 

  9. Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3(6):415–428. https://doi.org/10.1038/nrg816

    Article  CAS  PubMed  Google Scholar 

  10. Lauc G, Zoldoš V (2009) Epigenetic regulation of glycosylation could be a mechanism used by complex organisms to compete with microbes on an evolutionary scale. Med Hypotheses 73(4):510–512. https://doi.org/10.1016/j.mehy.2009.03.059

    Article  CAS  PubMed  Google Scholar 

  11. Cooper DN (1983) Eukaryotic DNA methylation. Hum Genet 64(4):315–333. https://doi.org/10.1007/BF00292363

    Article  CAS  PubMed  Google Scholar 

  12. Ohm JE, McGarvey KM, Yu X et al (2007) A stem cell–like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat Genet 39(2):237–242. https://doi.org/10.1038/ng1972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Meissner A, Mikkelsen TS, Gu H et al (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454(7205):766–770. https://doi.org/10.1038/nature07107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rodríguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17(3):330–339. https://doi.org/10.1038/nm.2305

    Article  CAS  PubMed  Google Scholar 

  15. Mashimo M, Kato J, Moss J (2013) ADP-ribosyl-acceptor hydrolase 3 regulates poly (ADP-ribose) degradation and cell death during oxidative stress. Proc Natl Acad Sci 110(47):18964–18969. https://doi.org/10.1073/pnas.1312783110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pasquinelli AE (2012) MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 13(4):271–282. https://doi.org/10.1038/nrg3162

    Article  CAS  PubMed  Google Scholar 

  17. Sun W, Liu Y, Glazer CA et al (2010) TKTL1 Is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1 stabilization. Clin Cancer Res 16(3):857–866. https://doi.org/10.1158/1078-0432.CCR-09-2604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Barbano R, Muscarella LA, Pasculli B et al (2013) Aberrant Keap1 methylation in breast cancer and association with clinicopathological features. Epigenetics 8(1):105–112. https://doi.org/10.4161/epi.23319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chao C, Chi M, Preciado M et al (2013) Methylation markers for prostate cancer prognosis: a systematic review. Cancer Causes Control 24(9):1615–1641. https://doi.org/10.1007/s10552-013-0249-2

    Article  PubMed  Google Scholar 

  20. Mehta A, Dobersch S, Romero-Olmedo AJ et al (2015) Epigenetics in lung cancer diagnosis and therapy. Cancer Metastasis Rev 34(2):229–241. https://doi.org/10.1007/s10555-015-9563-3

    Article  CAS  PubMed  Google Scholar 

  21. Liu X, Brenner DA (2016) DNA methylation controls liver fibrogenesis. Nat Rev Gastroenterol Hepatol 13(3):126–128. https://doi.org/10.1038/nrgastro.2016.16

    Article  CAS  PubMed  Google Scholar 

  22. Cecotka A, Polanska J (2018) Region-specific methylation profiling in acute myeloid leukemia. Interdiscip Sci Comput Life Sci 10(1):33–42. https://doi.org/10.1007/s12539-018-0285-4

    Article  CAS  Google Scholar 

  23. Klughammer J, Kiesel B, Roetzer T et al (2018) The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space. Nat Med 24(10):1611–1624. https://doi.org/10.1038/s41591-018-0156-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Satelli A, Rao US (2011) Galectin-1 is silenced by promoter hypermethylation and its re-expression induces apoptosis in human colorectal cancer cells. Cancer Lett 301(1):38–46. https://doi.org/10.1016/j.canlet.2010.10.027

    Article  CAS  PubMed  Google Scholar 

  25. Krawczyk J, Keane N, Freeman CL et al (2013) 5-Azacytidine for the treatment of myelodysplastic syndromes. Expert Opin Pharmacother 14(9):1255–1268. https://doi.org/10.1517/14656566.2013.794222

    Article  CAS  PubMed  Google Scholar 

  26. Ahmed H, Banerjee PP, Vasta GR (2007) Differential expression of galectins in normal, benign and malignant prostate epithelial cells: Silencing of galectin-3 expression in prostate cancer by its promoter methylation. Biochem Biophys Res Commun 358(1):241–246. https://doi.org/10.1016/j.bbrc.2007.04.114

    Article  CAS  PubMed  Google Scholar 

  27. Ahmed H, Cappello F, Rodolico V et al (2009) Evidence of heavy methylation in the galectin 3 promoter in early stages of prostate adenocarcinoma: development and validation of a methylated marker for early diagnosis of prostate cancer. Transl Oncol 2(3):146–156. https://doi.org/10.1593/tlo.09118

    Article  PubMed  PubMed Central  Google Scholar 

  28. Keller S, Angrisano T, Florio E et al (2013) DNA methylation state of the galectin-3 gene represents a potential new marker of thyroid malignancy. Oncol Lett 6(1):86–90. https://doi.org/10.3892/ol.2013.1312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Demers M, Couillard J, Giglia-Mari G et al (2009) Increased galectin-7 gene expression in lymphoma cells is under the control of DNA methylation. Biochem Biophys Res Commun 387(3):425–429. https://doi.org/10.1016/j.bbrc.2009.07.015

    Article  CAS  PubMed  Google Scholar 

  30. Kim S-J, Hwang J-A, Ro JY et al (2013) Galectin-7 is epigenetically-regulated tumor suppressor in gastric cancer. Oncotarget 4(9):1461–1471. https://doi.org/10.18632/oncotarget.1219

  31. Jung G, Hernández-Illán E, Moreira L et al (2020) Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat Rev Gastroenterol Hepatol 17(2):111–130. https://doi.org/10.1038/s41575-019-0230-y

    Article  PubMed  PubMed Central  Google Scholar 

  32. Fraga MF, Ballestar E, Villar-Garea A et al (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37(4):391–400. https://doi.org/10.1038/ng1531

    Article  CAS  PubMed  Google Scholar 

  33. Moreno DA, Scrideli CA, Cortez MAA et al (2010) Research paper: differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia: HDAC Expression in Paediatric ALL. Br J Haematol 150(6):665–673. https://doi.org/10.1111/j.1365-2141.2010.08301.x

    Article  CAS  PubMed  Google Scholar 

  34. Tao Y-F, Pang L, Du X-J et al (2013) Differential mRNA expression levels of human histone-modifying enzymes in normal karyotype B cell pediatric acute lymphoblastic leukemia. Int J Mol Sci 14(2):3376–3394. https://doi.org/10.3390/ijms14023376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Choi J-H, Kwon HJ, Yoon B-I et al (2001) Expression profile of histone deacetylase 1 in gastric cancer tissues. Jpn J Cancer Res 92(12):1300–1304. https://doi.org/10.1111/j.1349-7006.2001.tb02153.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Halkidou K, Gaughan L, Cook S et al (2004) Upregulation and Nuclear Recruitment of HDAC1 in Hormone Refractory Prostate Cancer. Prostate 59(2):177–189. https://doi.org/10.1002/pros.20022

    Article  CAS  PubMed  Google Scholar 

  37. Wilson AJ, Byun D-S, Popova N et al (2006) Histone Deacetylase 3 (HDAC3) and Other Class I HDACs Regulate Colon Cell Maturation and p21 Expression and Are Deregulated in Human Colon Cancer. J Biol Chem 281(19):13548–13558. https://doi.org/10.1074/jbc.M510023200

    Article  CAS  PubMed  Google Scholar 

  38. Zhang Z, Yamashita H, Toyama T et al (2005) Quantitation of HDAC1 mRNA Expression in Invasive Carcinoma of the Breast*. Breast Cancer Res Treat 94(1):11–16. https://doi.org/10.1007/s10549-005-6001-1

    Article  CAS  PubMed  Google Scholar 

  39. Armenta-Castro E, Reyes-Vallejo T, Máximo-Sánchez D et al (2020) Histone H3K9 and H3K14 acetylation at the promoter of the LGALS9 gene is associated with mRNA levels in cervical cancer cells. FEBS Open Bio 10(11):2305–2315. https://doi.org/10.1002/2211-5463.12973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Garzon R, Calin GA, Croce CM (2009) MicroRNAs in cancer. Annu Rev Med 60(1):167–179. https://doi.org/10.1146/annurev.med.59.053006.104707

    Article  CAS  PubMed  Google Scholar 

  41. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5(7):522–531. https://doi.org/10.1038/nrg1379

    Article  CAS  PubMed  Google Scholar 

  42. Bruce JP, Hui ABY, Shi W, et al (2015) Identification of a microRNA signature associated with risk of distant metastasis in nasopharyngeal carcinoma. Oncotarget 6(6):4537–4550. https://doi.org/10.18632/oncotarget.3005

  43. Deng S, Calin GA, Croce CM et al (2008) Mechanisms of microRNA deregulation in human cancer. Cell Cycle 7(17):2643–2646. https://doi.org/10.4161/cc.7.17.6597

    Article  CAS  PubMed  Google Scholar 

  44. Valoczi A (2004) Sensitive and specific detection of microRNAs by northern blot analysis using LNA-modified oligonucleotide probes. Nucleic Acids Res 32(22):e175–e175. https://doi.org/10.1093/nar/gnh171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Takahashi R, Prieto-Vila M, Kohama I et al (2019) Development of miRNA-based therapeutic approaches for cancer patients. Cancer Sci 110(4):1140–1147. https://doi.org/10.1111/cas.13965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Baer C, Squadrito ML, Laoui D et al (2016) Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity. Nat Cell Biol 18(7):790–802. https://doi.org/10.1038/ncb3371

    Article  CAS  PubMed  Google Scholar 

  47. Lu W, Wang J, Yang G, et al (2017) Posttranscriptional regulation of Galectin-3 by miR-128 contributes to colorectal cancer progression. Oncotarget 8(9):15242–15251. https://doi.org/10.18632/oncotarget.14839

  48. Ramasamy S, Duraisamy S, Barbashov S et al (2007) The MUC1 and Galectin-3 Oncoproteins Function in a MicroRNA-Dependent Regulatory Loop. Mol Cell 27(6):992–1004. https://doi.org/10.1016/j.molcel.2007.07.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Yang Q, Hou C, Huang D et al (2017) miR-455-5p functions as a potential oncogene by targeting galectin-9 in colon cancer. Oncol Lett 13(3):1958–1964. https://doi.org/10.3892/ol.2017.5608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kang HG, Kim D-H, Kim S-J, et al (2016) Galectin-3 supports stemness in ovarian cancer stem cells by activation of the Notch1 intracellular domain. Oncotarget 7(42):68229–68241. https://doi.org/10.18632/oncotarget.11920

  51. Bieg D, Sypniewski D, Nowak E et al (2019) MiR-424-3p suppresses galectin-3 expression and sensitizes ovarian cancer cells to cisplatin. Arch Gynecol Obstet 299(4):1077–1087. https://doi.org/10.1007/s00404-018-4999-7

    Article  CAS  PubMed  Google Scholar 

  52. Zhang J, Zhao X, Zhang J et al (2018) Circular RNA hsa_circ_0023404 exerts an oncogenic role in cervical cancer through regulating miR-136/TFCP2/YAP pathway. Biochem Biophys Res Commun 501(2):428–433. https://doi.org/10.1016/j.bbrc.2018.05.006

    Article  CAS  PubMed  Google Scholar 

  53. Meng S, Zhou H, Feng Z et al (2017) CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer 16(1):94. https://doi.org/10.1186/s12943-017-0663-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hansen TB, Jensen TI, Clausen BH et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388. https://doi.org/10.1038/nature11993

    Article  CAS  PubMed  Google Scholar 

  55. Qiu B, Zhang P, Xiong D et al (2019) CircRNA fibroblast growth factor receptor 3 promotes tumor progression in non-small cell lung cancer by regulating Galectin-1-AKT/ERK1/2 signaling. J Cell Physiol 234(7):11256–11264. https://doi.org/10.1002/jcp.27783

    Article  CAS  PubMed  Google Scholar 

  56. Sun X, Cui M, Zhang A et al (2016) MiR-548c impairs migration and invasion of endometrial and ovarian cancer cells via downregulation of Twist. J Exp Clin Cancer Res 35(1):10. https://doi.org/10.1186/s13046-016-0288-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chen X, Chen Y, Hu Q et al (2018) MiR-548c inhibits lung cancer cell proliferation through suppression of Galectin-3-mediated TLR4 signaling pathway. Int J Clin Exp Med 11(2):581–592

    Google Scholar 

  58. Yang Q, Jiang W, Zhuang C et al (2015) microRNA-22 downregulation of galectin-9 influences lymphocyte apoptosis and tumor cell proliferation in liver cancer. Oncol Rep 34(4):1771–1778. https://doi.org/10.3892/or.2015.4167

    Article  CAS  PubMed  Google Scholar 

  59. Tadokoro T, Fujihara S, Chiyo T et al (2017) Induction of apoptosis by Galectin-9 in liver metastatic cancer cells: in vitro study. Int J Oncol 51(2):607–614. https://doi.org/10.3892/ijo.2017.4053

    Article  CAS  PubMed  Google Scholar 

  60. Wu H, Song S, Yan A et al (2020) RACK1 promotes the invasive activities and lymph node metastasis of cervical cancer via galectin-1. Cancer Lett 469:287–300. https://doi.org/10.1016/j.canlet.2019.11.002

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the Council of Scientific and Industrial Research/University Commission Grants (CSIR/UGC) (File No.09/1197(0002)/2019-EMR-I).

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Authors and Affiliations

  1. Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Basni Industrial Area, MIA 2nd Phase, Basni, Jodhpur, Rajasthan, 342005, India

    Ashita Gadwal, Anupama Modi, Manoj Khokhar, Mithu Banerjee & Purvi Purohit

  2. Department of Oncosurgery, All India Institute of Medical Sciences, Jodhpur, Basni Industrial Area, MIA 2nd Phase, Basni, Jodhpur, Rajasthan, 342005, India

    Jeewan Ram Vishnoi

  3. Department of General Surgery, All India Institute of Medical Sciences, Jodhpur, Basni Industrial Area, MIA 2nd Phase, Basni, Jodhpur, Rajasthan, 342005, India

    Ramkaran Choudhary

  4. Department of Pathology, All India Institute of Medical Sciences, Jodhpur, Basni Industrial Area, MIA 2nd Phase, Basni, Jodhpur, Rajasthan, 342005, India

    Poonam Elhence

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  1. Ashita Gadwal
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  2. Anupama Modi
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  3. Manoj Khokhar
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  4. Jeewan Ram Vishnoi
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  5. Ramkaran Choudhary
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  7. Mithu Banerjee
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  8. Purvi Purohit
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Contributions

Idea: Dr. PP, AG. Literature search: AG. Drafted: AG, Dr PP. Critically revised: Dr. PP, AG, AM, MK, JRV, RC, PE, MB.

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Correspondence to Purvi Purohit.

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Gadwal, A., Modi, A., Khokhar, M. et al. Critical appraisal of epigenetic regulation of galectins in cancer. Int J Clin Oncol 27, 35–44 (2022). https://doi.org/10.1007/s10147-021-02048-x

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