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rs6426881 in the 3'-UTR of PBX1 is involved in breast and gastric cancers via altering the binding potential of miR-522-3p

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Abstract

Background

Breast and gastric cancers are the most important diseases that lead to cancer death and social healthcare challenge. Overexpression of PBX1, a proto-oncogene, is correlated with the progression and metastasis of various cancers. For the first time, in this study the researchers evaluated the relationship between rs6426881, affecting miR-522-3p binding to the PBX1, with breast and gastric cancers.

Methods and results

The Microarray analysis was performed for finding the relative expression level of PBX1 and hsa-miR-522-3p, based on high throughput experiments. The GSE54397, GSE112369, GSE10810, GSE241585.ER, GSE24185.PR, GSE68373, and GSE38167 datasets were analyzed. A case-control study was carried out in 123 Iranian suffering from breast cancer and 132 participants as control samples as well as 130 people suffering from gastric cancer and 54 people as control group members. SNP rs6426881 in the 3′-UTR of PBX1 was genotyped by the High-Resolution Melting (HRM) method. Association analysis revealed that rs6426881 is correlated with Estrogen and Progesterone receptors, grade, and stage of breast cancer. Furthermore, a significant relationship was observed between the genotypes and blood groups in gastric cancer, while the distribution of alleles was significantly related to smoking, status of the primary tumor, and metastasis (Chi-Square P < 0.05). Finally, Bioinformatics analyses suggested that rs6426881 contains binding sites for miR-522-3p in the 3′-UTR of PBX1 transcript. The finding suggested that TT genotype is associated with poor prognosis in breast and gastric cancer.

Conclusions

The rs6426881 T allele at PBX1 3′-UT is significantly related to breast and gastric cancers by altering the regulatory affinity of miR-522-3p to PBX1 3′-UTR and may be suggested as a novel prognostic biomarker for the diseases.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

References

  1. Ashiq MG (2019) Laser-irradiated gold nanoparticles for breast cancer therapy. Mod Phys Lett B 33(19):1950217. https://doi.org/10.1142/S0217984919502178

    Article  CAS  Google Scholar 

  2. Wang YW, Zhang W, Ma R (2018) Bioinformatic identification of chemoresistance-associated microRNAs in breast cancer based on microarray data. Oncol Rep 39(3):1003–1010. https://doi.org/10.3892/or.2018.6205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Akbari ME, Sayad S, Sayad S, Khayamzadeh M, Shojaee L, Shormeji Z, Amiri M (2017) Breast cancer status in Iran: statistical analysis of 3010 cases between 1998 and 2014. Int J Breast Cancer. https://doi.org/10.1155/2017/2481021

    Article  PubMed  PubMed Central  Google Scholar 

  4. Farhood B, Geraily G, Alizadeh A (2018) Incidence and mortality of various cancers in Iran and compare to other countries: a review article. Iran J Public Health 47(3):309

    PubMed  PubMed Central  Google Scholar 

  5. Nafissi N, Khayamzadeh M, Zeinali Z, Pazooki D, Hosseini M, Akbari ME (2018) Epidemiology and histopathology of breast cancer in Iran versus other middle Eastern countries. Middle East J Cancer 9(3):243–251. https://doi.org/10.30476/mejc.2018.42130

    Article  Google Scholar 

  6. Ferreira RM, Pereira-Marques J, Pinto-Ribeiro I, Costa JL, Carneiro F, Machado JC, Figueiredo C (2018) Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut 67(2):226–236. https://doi.org/10.1136/gutjnl-2017-314205

    Article  CAS  PubMed  Google Scholar 

  7. Coburn N, Cosby R, Klein L, Knight G, Malthaner R, Mamazza J, Mercer CD, Ringash J (2018) Staging and surgical approaches in gastric cancer: a systematic review. Cancer Treat Rev 63:104–115. https://doi.org/10.3747/co.24.3736

    Article  PubMed  Google Scholar 

  8. Kim ST, Cristescu R, Bass AJ, Kim KM, Odegaard JI, Kim K, Liu XQ, Sher X, Jung H, Lee M, Lee S (2018) Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med 24(9):1449–1458. https://doi.org/10.1038/s41591-018-0101-z

    Article  CAS  PubMed  Google Scholar 

  9. Boreiri M, Samadi F, Etemadi A, Babaei M, Ahmadi E, Sharifi AH, Nikmanesh A, Houshiar A, Pourfarzi F, Yazdanbod A, Alimohammadian M (2013) Gastric cancer mortality in a high incidence area: long-term follow-up of Helicobacter pylori-related precancerous lesions in the general population. Arch Iran Med 16(6):343

    PubMed  PubMed Central  Google Scholar 

  10. Ghaffari HR, Yunesian M, Nabizadeh R, Nasseri S, Sadjadi A, Pourfarzi F, Poustchi H, Eshraghian A (2019) Environmental etiology of gastric cancer in Iran: a systematic review focusing on drinking water, soil, food, radiation, and geographical conditions. Environ Sci Pollut Res 26(11):10487–10495. https://doi.org/10.1007/s11356-019-04493-8

    Article  CAS  Google Scholar 

  11. Safaee A, Moghimi-Dehkordi B, Fatemi SR, Maserat E, Zali MR (2011) Family history of cancer and risk of gastric cancer in Iran. Asian Pac J Cancer Prev 12(11):3117–3120

    CAS  PubMed  Google Scholar 

  12. Khanzadeh H, Khoshdel AR, Irvani S, Majidzadeh-A K, Soleimani M (2019) Genetic polymorphism of Thr241Met and other risk factors related with gastric cancer in Iranian military population: a pilot case-control study. J Arch Mil Med. https://doi.org/10.5812/jamm.92673

    Article  Google Scholar 

  13. Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, Park B, Nam BH (2018) Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med 378(12):1085–1095. https://doi.org/10.1056/NEJMoa1708423

    Article  CAS  PubMed  Google Scholar 

  14. Huang BF, Tzeng HE, Chen PC, Wang CQ, Su CM, Wang Y, Hu GN, Zhao YM, Wang Q, Tang CH (2018) HMGB1 genetic polymorphisms are biomarkers for the development and progression of breast cancer. Int J Med Med Sci 15(6):580. https://doi.org/10.7150/ijms.23462

    Article  CAS  Google Scholar 

  15. Deng N, Zhou H, Fan H, Yuan Y (2017) Single nucleotide polymorphisms and cancer susceptibility. Oncotarget 8(66):110635. https://doi.org/10.18632/oncotarget.22372

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zhang J, Wei B, Hu H, Liu F, Tu Y, He F (2018) The association between differentially expressed micro RNAs in breast cancer cell lines and the micro RNA-205 gene polymorphism in breast cancer tissue. Oncol Lett 15(2):2139–2146. https://doi.org/10.3892/ol.2017.7550

    Article  CAS  PubMed  Google Scholar 

  17. Hubner RA, Houlston RS (2017) Single nucleotide polymorphisms and cancer susceptibility. In: Coleman WB, Tsongalis GJ (eds) The molecular basis of human cancer. Humana Press, New York, pp 231–239

    Chapter  Google Scholar 

  18. Song X, Zhong H, Wu Q, Wang M, Zhou J, Zhou Y, Lu X, Ying B (2017) Association between SNPs in microRNA machinery genes and gastric cancer susceptibility, invasion, and metastasis in Chinese Han population. Oncotarget 8(49):86435. https://doi.org/10.18632/oncotarget.21199

    Article  PubMed  PubMed Central  Google Scholar 

  19. Xia J, Sun R (2017) Association between the polymorphisms in XPG gene and gastric cancer susceptibility in Chinese populations: a PRISMA-compliant meta-analysis. Medicine. https://doi.org/10.1097/MD.0000000000008213

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zhi P, Shi J, Liu F (2017) Genetic variations at 8q24 and gastric cancer susceptibility: a meta-analysis study. PLoS ONE 12(12):e0188774. https://doi.org/10.1371/journal.pone.0188774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Neininger K, Marschall T, Helms V (2019) SNP and indel frequencies at transcription start sites and canonical and alternative translation initiation sites in the human genome. PLoS ONE 14(4):e0214816. https://doi.org/10.1371/journal.pone.0214816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bartonicek N, Clark MB, Quek XC, Torpy JR, Pritchard AL, Maag JL, Gloss BS, Crawford J, Taft RJ, Hayward NK, Montgomery GW (2017) Intergenic disease-associated regions are abundant in novel transcripts. Genome Biol 18(1):1–6. https://doi.org/10.1186/s13059-017-1363-3

    Article  CAS  Google Scholar 

  23. Park JT, Shih IM, Wang TL (2008) Identification of Pbx1, a potential oncogene, as a Notch3 target gene in ovarian cancer. Cancer Res 68(21):8852–8860. https://doi.org/10.1158/0008-5472.CAN-08-0517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Liu Y, Xu X, Lin P, He Y, Zhang Y, Cao B, Zhang Z, Sethi G, Liu J, Zhou X, Mao X (2019) Inhibition of the deubiquitinase USP9x induces pre-B cell homeobox 1 (PBX1) degradation and thereby stimulates prostate cancer cell apoptosis. J Biol Chem 294(12):4572–4582. https://doi.org/10.1074/jbc.RA118.006057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Reis ST, Leite KR, Marchini GS, Guimarães RM, Viana NI, Pimenta RC, Torricelli FC, Danilovic A, Vicentini FC, Nahas WC, Srougi M (2019) Polymorphism in the PBX 1 gene is related to cystinuria in Brazilian families. J Cell Mol Med 23(2):1593–1597. https://doi.org/10.1111/jcmm.13981

    Article  CAS  PubMed  Google Scholar 

  26. Ma W, Li Y, Wang M, Li H, Su T, Li Y, Wang S (2015) Associations of polymorphisms in WNT9B and PBX1 with Mayer-Rokitansky-Küster-Hauser syndrome in Chinese Han. PLoS ONE 10(6):e0130202. https://doi.org/10.1371/journal.pone.0130202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ban JY, Kang SA, Jung KH, Kim HJ, Uhm YK, Kim SK, Yim SV, Choe BK, Hong SJ, Seong YH, Koh IS (2008) The association of PBX1 polymorphisms with overweight/obesity and metabolic alterations in the Korean population. Nutr Res Pract 2(4):289. https://doi.org/10.4162/nrp.2008.2.4.289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rafiq S, Tapper W, Collins A, Khan S, Politopoulos I, Gerty S, Blomqvist C, Couch FJ, Nevanlinna H, Liu J, Eccles D (2013) Identification of inherited genetic variations influencing prognosis in early-onset breast cancer. Cancer Res 73(6):1883–1891. https://doi.org/10.1158/0008-5472.CAN-12-3377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wahid F, Shehzad A, Khan T, Kim YY (2010) MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta Mol Cell Res 1803(11):1231–1243. https://doi.org/10.1016/j.bbamcr.2010.06.013

    Article  CAS  Google Scholar 

  30. Palanichamy JK, Rao DS (2014) miRNA dysregulation in cancer: towards a mechanistic understanding. Front Genet 5:54. https://doi.org/10.3389/fgene.2014.00054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Walayat A, Yang M, Xiao D (2018) Therapeutic implication of miRNA in human disease. In: Sharad S, Kapur S (eds) Antisense therapy. IntechOpen, London. https://doi.org/10.5772/intechopen.82738

    Chapter  Google Scholar 

  32. Loh HY, Norman BP, Lai KS, Rahman NM, Alitheen NB, Osman MA (2019) The regulatory role of microRNAs in breast cancer. Int J Mol Sci 20(19):4940. https://doi.org/10.3390/ijms20194940

    Article  CAS  PubMed Central  Google Scholar 

  33. Zhong S, Li W, Chen Z, Xu J, Zhao J (2013) MiR-222 and miR-29a contribute to the drug-resistance of breast cancer cells. Gene 531(1):8–14. https://doi.org/10.1016/j.gene.2013.08.062

    Article  CAS  PubMed  Google Scholar 

  34. Yu DD, Lv MM, Chen WX, Zhong SL, Zhang XH, Chen L, Ma TF, Tang JH, Zhao JH (2015) Role of miR-155 in drug resistance of breast cancer. Tumor Biol 36(3):1395–1401. https://doi.org/10.1007/s13277-015-3263-z

    Article  CAS  Google Scholar 

  35. Li Y, Tian Z, Tan Y, Lian G, Chen S, Chen S, Li J, Li X, Huang K, Chen Y (2020) Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer. Mol Cancer 19(1):1–4. https://doi.org/10.1186/s12943-020-01229-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gu Y, Fei Z, Zhu R (2020) miR-21 modulates cisplatin resistance of gastric cancer cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway. Anticancer Drugs 31(4):385–393. https://doi.org/10.1097/CAD.0000000000000886

    Article  CAS  PubMed  Google Scholar 

  37. Sætrom P, Biesinger J, Li SM, Smith D, Thomas LF, Majzoub K, Rivas GE, Alluin J, Rossi JJ, Krontiris TG, Weitzel J (2009) A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Cancer Res 69(18):7459–7465. https://doi.org/10.1158/0008-5472.CAN-09-1201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Shuai F, Wang B, Dong S (2018) miR-522-3p promotes tumorigenesis in human colorectal cancer via targeting bloom syndrome protein. Oncol Res Featur Preclin Clin Cancer Ther 26(7):1113–1121

    Google Scholar 

  39. Zhang T, Hu Y, Ju J, Hou L, Li Z, Xiao D, Li Y, Yao J, Wang C, Zhang Y, Zhang L (2016) Downregulation of miR-522 suppresses proliferation and metastasis of non-small cell lung cancer cells by directly targeting DENN/MADD domain containing 2D. Sci Rep 6(1):1–2. https://doi.org/10.1038/srep19346

    Article  CAS  Google Scholar 

  40. Słomka M, Sobalska-Kwapis M, Wachulec M, Bartosz G, Strapagiel D (2017) High resolution melting (HRM) for high-throughput genotyping—limitations and caveats in practical case studies. Int J Mol Sci 18(11):2316. https://doi.org/10.3390/ijms18112316

    Article  CAS  PubMed Central  Google Scholar 

  41. Huynh LH, Bui PT, Nguyen TT, Nguyen HT (2017) Developing a high-resolution melting method for genotyping and predicting the association of SNP rs353291 with breast cancer in the Vietnamese population. Biomed Res Ther 4(12):1812–1831. https://doi.org/10.15419/bmrat.v4i12.387

    Article  Google Scholar 

  42. Vorn R, Ryu E, Srun S, Chang S, Suh I, Kim W (2020) Breast and cervical cancer screening for risk assessment in Cambodian women. J Obstet Gynaecol Res 40(3):395–400. https://doi.org/10.1080/01443615.2019.1633515

    Article  Google Scholar 

  43. Tirado CA, Shabsovich D, Yeh L, Pullarkat ST, Yang L, Kallen M, Rao N (2015) A (1; 19) translocation involving TCF3-PBX1 fusion within the context of a hyperdiploid karyotype in adult B-ALL: a case report and review of the literature. Biomark Res 3(1):1–6. https://doi.org/10.1186/s40364-015-0029-0

    Article  Google Scholar 

  44. He C, Wang Z, Zhang L, Yang L, Li J, Chen X, Zhang J, Chang Q, Yu Y, Liu B, Zhu Z (2017) A hydrophobic residue in the TALE homeodomain of PBX1 promotes the epithelial-to-mesenchymal transition of gastric carcinoma. Oncotarget 8(29):46818. https://doi.org/10.18632/oncotarget.17473

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ritchie ME, Phipson B, Wu DI, Hu Y, Law CW, Shi W, Smyth GK (2015) limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43(7):e47. https://doi.org/10.1093/nar/gkv007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ono H, Ogasawara O, Okubo K, Bono H (2017) RefEx, a reference gene expression dataset as a web tool for the functional analysis of genes. Sci Data 4(1):1–1. https://doi.org/10.1038/sdata.2017.105

    Article  CAS  Google Scholar 

  47. Maksimovic J, Oshlack A, Phipson B (2021) Gene set enrichment analysis for genome-wide DNA methylation data. Genome Biol 22(1):1–26. https://doi.org/10.1186/s13059-021-02388-x

    Article  CAS  Google Scholar 

  48. Qin X, Jiang M, Zhao Y, Gong J, Su H, Yuan F, Fang K, Yuan X, Yu X, Dong H, Lu F (2020) Berberine protects against diabetic kidney disease via promoting PGC-1α-regulated mitochondrial energy homeostasis. Br J Pharmacol 177(16):3646–3661. https://doi.org/10.1111/bph.14935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran

    Maryam Mohammadi & Ali Salehzadeh

  2. Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran

    Soheila Talesh Sasani

  3. Rice Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO), Rasht, Iran

    Alireza Tarang

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  1. Maryam Mohammadi
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  2. Ali Salehzadeh
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Contributions

Conceptualization: MM and AS, STS; Methodology: MM and AS; Formal analysis and investigation: MM, AS, STS and AT; Writing—Original Draft Preparation: MM, AS; Editing: AS, STS and AT; Resources: MM; Supervision: AS, STS and AT.

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Correspondence to Ali Salehzadeh.

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This experimental study was approved by the animal care and use committee at the Islamic Azad University, Rasht branch (Approval ID: IR.IAU.RASHT.REC.1398.056).

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Informed consent was obtained from all individual participants included in the study and the study was carried out with the approval of the Ethical Committee of Islamic Azad University of Rasht.

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Mohammadi, M., Salehzadeh, A., Talesh Sasani, S. et al. rs6426881 in the 3'-UTR of PBX1 is involved in breast and gastric cancers via altering the binding potential of miR-522-3p. Mol Biol Rep 48, 7405–7414 (2021). https://doi.org/10.1007/s11033-021-06756-5

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