Experimental and Bioinformatic Clues to the Potential Roles of hsa_circ_0013958 and hsa_circ_0003028 in Clinopathophysiology of Breast Cancer
DOI:
https://doi.org/10.31661/gmj.v10i.2064Keywords:
Breast Cancer; hsa_circ_0013958; hsa_circ_0003028; ceRNA; circRNAsAbstract
Background: Circular RNAs (circRNAs), covalently closed single-stranded non-coding RNAs (ncRNAs), play pivotal roles in development and progression of breast cancer (BC). Although the roles of hsa_circ_0013958 and hsa_circ_0003028 in some malignancies have been explored, their function and expression in breast tumors are still unknown. This study was aimed to bioinformatically and experimentally evaluates the expression and potential function of hsa_circ_0013958 and hsa_circ_0003028 in BC. Materials and Methods: The quantitative real-time PCR method was used to determine the expression of hsa_circ_0013958 and hsa_circ_0003028 in 50 tumor samples and matched adjacent non-cancerous tissues. Besides, we used bioinformatic approaches to identify potentially important competing endogenous RNA (ceRNA) networks that are regulated by these circRNAs using some databases and software tools. Results: The hsa_circ_0013958 was significantly down-regulated in breast tumors compared with adjacent normal tissues, while the hsa_circ_0003028 had an upregulated pattern. Interestingly, it is found the higher expression of hsa_circ_0013958 showed association with a lack of use of hair dye as well as age at menarche ≥14 years in subjects. On the other hand, hsa_circ_0003028 expression was meaningfully related to age at first full-term pregnancy, antiperspirants use, and regular menstruation. Next, we found that these two circRNAs can potentially regulate some circRNAs-mediated miRNA sponge regulatory networks. Conclusion: The current work indicated that the hsa_circ_0013958 and hsa_circ_0003028 had reverse expression patterns in breast tumors, and it seems that they play key roles in the physiopathology of this cancer through potential key regulatory ceRNA functions. However, further functional studies are needed to validate these bioinformatically observed roles. [GMJ.2021;10:e2064]
References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. https://doi.org/10.3322/caac.21551PMid:30620402 Consortium EP. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57-74. https://doi.org/10.1038/nature11247PMid:22955616 PMCid:PMC3439153 Al-Mansouri LJ, Alokail MS. Molecular basis of breast cancer. Saudi Med. 2006;27(1):9. Piao H-l, Ma L. Non-coding RNAs as regulators of mammary development and breast cancer. J Mammary Gland Biol. 2012;17(1):33-42. https://doi.org/10.1007/s10911-012-9245-5PMid:22350981 PMCid:PMC3686545 Hangauer MJ, Vaughn IW, McManus MT. Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet. 2013;9(6):e1003569. https://doi.org/10.1371/journal.pgen.1003569PMid:23818866 PMCid:PMC3688513 Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56(1):55-66. https://doi.org/10.1016/j.molcel.2014.08.019PMid:25242144 Suzuki H, Zuo Y, Wang J, Zhang MQ, Malhotra A, Mayeda A. Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing. Nucleic Acids Res. 2006;34(8):e63-e. https://doi.org/10.1093/nar/gkl151PMid:16682442 PMCid:PMC1458517 Han B, Chao J, Yao H. Circular RNA and its mechanisms in disease: from the bench to the clinic. Pharmacol Ther. 2018;187:31-44. https://doi.org/10.1016/j.pharmthera.2018.01.010PMid:29406246 Wu J, Qi X, Liu L, Hu X, Liu J, Yang J et al. Emerging epigenetic regulation of circular RNAs in human cancer. Mol Ther Nucleic Acids. 2019;16:589-96. https://doi.org/10.1016/j.omtn.2019.04.011PMid:31082792 PMCid:PMC6517616 Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384-8. https://doi.org/10.1038/nature11993PMid:23446346 Wang X, Fang L. Advances in circular RNAs and their roles in breast Cancer. J Exp Clin Cancer Res. 2018;37(1):206. https://doi.org/10.1186/s13046-018-0870-8PMid:30157902 PMCid:PMC6116371 Glažar P, Papavasileiou P, Rajewsky N. circBase: a database for circular RNAs. Rna. 2014;20(11):1666-70. https://doi.org/10.1261/rna.043687.113PMid:25234927 PMCid:PMC4201819 Zhu X, Wang X, Wei S, Chen Y, Chen Y, Fan X et al. hsa_circ_0013958: a circular RNA and potential novel biomarker for lung adenocarcinoma. FEBS J. 2017;284(14):2170-82. https://doi.org/10.1111/febs.14132PMid:28685964 Pei C, Wang H, Shi C, Zhang C, Wang M. CircRNA hsa_circ_0013958 may contribute to the development of ovarian cancer by affecting epithelial mesenchymal transition and apoptotic signaling pathways. J Clin Lab Anal. 2020:e23292. https://doi.org/10.1002/jcla.23292 He Q, Yan D, Dong W, Bi J, Huang L, Yang M et al. circRNA circFUT8 upregulates Krüpple-like factor 10 to inhibit the metastasis of bladder Cancer via sponging miR-570-3p. Mol Ther Oncolytics. 2020;16:172-87. https://doi.org/10.1016/j.omto.2019.12.014PMid:32072011 PMCid:PMC7013148 Li S, Gu H, Huang Y, Peng Q, Zhou R, Yi P et al. Circular RNA 101368/miR-200a axis modulates the migration of hepatocellular carcinoma through HMGB1/RAGE signaling. Cell Cycle. 2018;17(19-20):2349-59. https://doi.org/10.1080/15384101.2018.1526599PMid:30265210 PMCid:PMC6237437 Chen L. Exploring the Role of Circulating MIR-134 In Breast Cancer Recurrence. 2019. Ahlin C, Lundgren C, Embretsén-Varro E, Jirström K, Blomqvist C, Fjällskog M-L. High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers. Breast Cancer Res Treat. 2017;164(3):667-78. https://doi.org/10.1007/s10549-017-4294-5PMid:28528450 PMCid:PMC5495873 Wang LL, Huang WW, Huang J, Huang RF, Li NN, Hong Y et al. Protective effect of hsa miR 570 3p targeting CD274 on triple negative breast cancer by blocking PI3K/AKT/mTOR signaling pathway. KAOHSIUNG J MED SCI. 2020. Sun S, Zhang W, Cui Z, Chen Q, Xie P, Zhou C et al. High mobility group box-1 and its clinical value in breast cancer. Onco Targets Ther. 2015;8:413. https://doi.org/10.2147/OTT.S73366PMid:25709474 PMCid:PMC4334343 Abdollahzadeh R, Daraei A, Mansoori Y, Sepahvand M, Amoli MM, Tavakkoly Bazzaz J. Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: a new look at hallmarks of breast cancer. J Cell Physiol. 2019;234(7):10080-100. https://doi.org/10.1002/jcp.27941PMid:30537129 Lambert M, Jambon S, Depauw S, David-Cordonnier M-H. Targeting transcription factors for cancer treatment. Molecules. 2018;23(6):1479. https://doi.org/10.3390/molecules23061479PMid:29921764 PMCid:PMC6100431 Orlandella FM, Mariniello RM, Mirabelli P, De Stefano AE, Iervolino PLC, Lasorsa VA et al. miR-622 is a novel potential biomarker of breast carcinoma and impairs motility of breast cancer cells through targeting NUAK1 kinase. Br J Cancer. 2020:1-12. https://doi.org/10.1038/s41416-020-0884-9PMid:32418991 PMCid:PMC7403386 Riggio M, Perrone MC, Polo ML, Rodriguez MJ, May M, Abba M et al. AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins. Sci Rep. 2017;7:44244. https://doi.org/10.1038/srep44244PMid:28287129 PMCid:PMC5347151 Leivonen S-K, Sahlberg KK, Mäkelä R, Due EU, Kallioniemi O, Børresen-Dale A-L et al. High-throughput screens identify microRNAs essential for HER2 positive breast cancer cell growth. Mol Oncol. 2014;8(1):93-104. https://doi.org/10.1016/j.molonc.2013.10.001PMid:24148764 PMCid:PMC5528509 Zhang Y, Liu J, Wang J. KRAS gene silencing inhibits the activation of PI3K-Akt-mTOR signaling pathway to regulate breast cancer cell epithelial-mesenchymal transition, proliferation and apoptosis. Eur Rev Med Pharmacol Sci. 2020;24(6):3085-96. Wang W, Hind T, Lam BWS, Herr DR. Sphingosine 1-phosphate signaling induces SNAI2 expression to promote cell invasion in breast cancer cells. FASEB J. 2019;33(6):7180-91. https://doi.org/10.1096/fj.201801635RPMid:30844311 Tang Y-Y, Zhao P, Zou T-N, Duan J-J, Zhi R, Yang S-Y et al. Circular RNA hsa_circ_0001982 promotes breast cancer cell carcinogenesis through decreasing miR-143. DNA Cell Biol. 2017;36(11):901-8. https://doi.org/10.1089/dna.2017.3862PMid:28933584 Chai C, Wu H, Wang B, Eisenstat DD, Leng RP. MicroRNA-498 promotes proliferation and migration by targeting the tumor suppressor PTEN in breast cancer cells. Carcinogenesis. 2018;39(9):1185-96. https://doi.org/10.1093/carcin/bgy092PMid:29985991 PMCid:PMC6148990 Pan Y, Jiao G, Wang C, Yang J, Yang W. MicroRNA-421 inhibits breast cancer metastasis by targeting metastasis associated 1. Biomed Pharmacother. 2016;83:1398-406. https://doi.org/10.1016/j.biopha.2016.08.058PMid:27583980 Parsa P, Parsa B. Effects of Reproductive Factors on Risk of Breast Cancer: A. Asian Pac J Cancer Prev. 2009;10:545-50. Henderson BE, Ross RK, Judd HL, Krailo MD, Pike MC. Do regular ovulatory cycles increase breast cancer risk? Cancer. 1985;56(5):1206-8. https://doi.org/10.1002/1097-0142(19850901)56:5 Clavel-Chapelon F. Cumulative number of menstrual cycles and breast cancer risk: results from the E3N cohort study of French women. Cancer Causes Control. 2002;13(9):831-8. https://doi.org/10.1023/A:1020684821837PMid:12462548 PMCid:PMC2001234 Mansoori Y, Tabei MB, Askari A, Izadi P, Daraei A, Bastami M et al. Expression levels of breast cancer related GAS 5 and LSINCT 5 lnc RNA s in cancer free breast tissue: Molecular associations with age at menarche and obesity. Breast J. 2018;24(6):876-82. https://doi.org/10.1111/tbj.13067PMid:29785740 Henderson BE, Feigelson HS. Hormonal carcinogenesis. Carcinogenesis. 2000;21(3):427-33. https://doi.org/10.1093/carcin/21.3.427PMid:10688862 Mansoori Y, Zendehbad Z, Askari A, Kouhpayeh A, Tavakkoly Bazzaz J, Nariman Saleh Fam Z et al. Breast cancer linked lncRNA u Eleanor is upregulated in breast of healthy women with lack or short duration of breastfeeding. J Cell Biochem. 2019;120(6):9869-76. https://doi.org/10.1002/jcb.28269PMid:30548300 Tamakoshi K, Yatsuya H, Wakai K, Suzuki S, Nishio K, Lin Y et al. Impact of menstrual and reproductive factors on breast cancer risk in Japan: results of the JACC study. Cancer Sci. 2005;96(1):57-62. https://doi.org/10.1111/j.1349-7006.2005.00010.xPMid:15649257 Russo J, Moral R, Balogh GA, Mailo D, Russo IH. The protective role of pregnancy in breast cancer. Breast Cancer Res. 2005;7(3):131. https://doi.org/10.1186/bcr1029PMid:15987443 PMCid:PMC1143568 Abdollahzadeh R, Mansoori Y, Azarnezhad A, Daraei A, Paknahad S, Mehrabi S et al. Expression and clinicopathological significance of AOC4P, PRNCR1, and PCAT1 lncRNAs in breast cancer. Pathol Res Pract. 2020;216(10):153131. https://doi.org/10.1016/j.prp.2020.153131PMid:32853955 Quan G, Li J. Circular RNAs: biogenesis, expression and their potential roles in reproduction. J Ovarian Res. 2018;11(1):9. https://doi.org/10.1186/s13048-018-0381-4PMid:29343298 PMCid:PMC5773157 Zhang C, Liu J, Lai M, Li J, Zhan J, Wen Q et al. Circular RNA expression profiling of granulosa cells in women of reproductive age with polycystic ovary syndrome. Arch Gynecol Obstet. 2019;300(2):431-40. https://doi.org/10.1007/s00404-019-05129-5PMid:30937532 PMCid:PMC6592967 Cheng J, Huang J, Yuan S, Zhou S, Yan W, Shen W et al. Circular RNA expression profiling of human granulosa cells during maternal aging reveals novel transcripts associated with assisted reproductive technology outcomes. PLoS One. 2017;12(6):e0177888. https://doi.org/10.1371/journal.pone.0177888PMid:28644873 PMCid:PMC5482436 Stiel L, Adkins Jackson PB, Clark P, Mitchell E, Montgomery S. A review of hair product use on breast cancer risk in African American women. Cancer Med. 2016;5(3):597-604. https://doi.org/10.1002/cam4.613PMid:26773423 PMCid:PMC4799949 Turesky RJ, Freeman JP, Holland RD, Nestorick DM, Miller DW, Ratnasinghe DL et al. Identification of aminobiphenyl derivatives in commercial hair dyes. Chem Res Toxicol. 2003;16(9):1162-73. https://doi.org/10.1021/tx030029rPMid:12971805 Hamblen EL, Cronin MT, Schultz TW. Estrogenicity and acute toxicity of selected anilines using a recombinant yeast assay. Chemosphere. 2003;52(7):1173-81. https://doi.org/10.1016/S0045-6535(03)00333-3 Bergman Å, Heindel JJ, Jobling S, Kidd K, Zoeller TR, Organization WH. State of the science of endocrine disrupting chemicals 2012. World Health Organization; 2013. https://doi.org/10.1016/j.toxlet.2012.03.020 Knower KC, To SQ, Leung Y-K, Ho S-M, Clyne CD. Endocrine disruption of the epigenome: a breast cancer link. Endocr Relat Cancer. 2014;21(2):T33. https://doi.org/10.1530/ERC-13-0513PMid:24532474 PMCid:PMC4504013 Diamanti-Kandarakis E, Bourguignon J-P, Giudice LC, Hauser R, Prins GS, Soto AM et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev. 2009;30(4):293-342. https://doi.org/10.1210/er.2009-0002PMid:19502515 PMCid:PMC2726844 Teng Y, Manavalan TT, Hu C, Medjakovic S, Jungbauer A, Klinge CM. Endocrine disruptors fludioxonil and fenhexamid stimulate miR-21 expression in breast cancer cells. Toxicol Sci. 2013;131(1):71-83. https://doi.org/10.1093/toxsci/kfs290PMid:23052036 PMCid:PMC3537134 Bhan A, Hussain I, Ansari KI, Bobzean SA, Perrotti LI, Mandal SS. Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo. J Steroid Biochem Mol Biol. 2014;141:160-70. https://doi.org/10.1016/j.jsbmb.2014.02.002PMid:24533973 PMCid:PMC4025971 Darbre PD. Aluminium, antiperspirants and breast cancer. J Inorg Biochem. 2005;99(9):1912-9. https://doi.org/10.1016/j.jinorgbio.2005.06.001PMid:16045991 Miller WR. Estrogen and breast cancer. Chapman & Hall; 1996. Pineau A, Fauconneau B, Sappino A-P, Deloncle R, Guillard O. If exposure to aluminium in antiperspirants presents health risks, its content should be reduced. J Trace Elem Med Biol. 2014;28(2):147-50. https://doi.org/10.1016/j.jtemb.2013.12.002PMid:24418462 Exley C. Aluminium and Alzheimer's Disease: The science that describes the link. Elsevier; 2001.