Potential Importance of miRNA Studies in Identification of Body Fluids: A Current Perspective

Year 2024, Volume: 38 Issue: 1, 80 - 92, 29.04.2024

Özlem Arat , Dilek Kaya-akyüzlü

Abstract

Although there are many findings at crime scenes that can be considered as evidence, biological samples are among the most important types of findings that reveal the relationship between the victim, the suspect and the crime scene; blood, menstrual blood, semen, vaginal secretions and saliva. Enzymatic, serological and microscopic methods have been used for years in the identification of biological fluids used in identification. Since biological samples are found at crime scenes in very small quantities and are often in a degraded state, identification of the samples becomes difficult. However, recently, forensic studies on the identification of body fluids with miRNAs, which are accepted as "non degraded evidence" due to their high stability, have reversed this situation. The general opinion in the majority of studies is that miRNAs can be used in the detection of body fluids. The modeling used during analysis is of great importance, especially in the correct analysis and classification of mixtures and risky samples due to their high sensitivity. As a result, according to the literature review, it has been suggested that the reason for not reaching definitive and common results in miRNA studies is the diversity or difference of analysis and modeling methods used in the studies. For future studies, it is recommended to conduct further research with a general and accepted common method. In this review, it is aimed to summarize various studies conducted recently on miRNAs from different aspects.

Keywords

Body fluid identification, micro RNA, forensic sciences, crime scene, qPCR.

Vücut Sıvılarının Kimliklendirilmesinde miRNA Çalışmalarının Potansiyel Önemi: Güncel Bir Bakış

Abstract

Olay yerlerinde, delil niteliği kazanabilecek olan birçok bulgu bulunsa da mağdur, şüpheli ve olay yeri ilişkisini ortaya çıkaran en önemli bulgu türlerinden olan biyolojik örnekler; kan, menstrual kan, meni, vajinal salgılar ve tükürüktür. Kimliklendirmede kullanılan biyolojik sıvıların tanımlanmasında enzimatik, serolojik ve mikroskobik yöntemler yıllardır kullanılmaktadır. Biyolojik örnekler olay yerlerinde çok küçük miktarlarda bulunduklarından ve çoğunlukla bozunmuş halde olduklarından dolayı örneklerin tespiti zorlaşmaktadır. Ancak son zamanlarda, yüksek stabiliteleri nedeniyle ‘’bozunmadan kalabilecek delil’’ niteliğinde kabul gören miRNA’lar ile vücut sıvılarının tanımlamasına yönelik yapılan adli çalışmalar bu durumu tersine çevirmektedir. Yapılan çalışmaların çoğunluğundaki genel görüş, miRNA’ların vücut sıvılarının tespitinde kullanılabilir olduğu yönündedir. Özellikle yüksek hassasiyetleri nedeniyle karışım halinde bulunan ve riskli örneklerin doğru bir şekilde analiz edilip sınıflandırılmasında, analiz yapılırken kullanılan modellemeler büyük önem taşımaktadır. Sonuç olarak yapılan literatür taramalarına göre, miRNA çalışmalarında kesin ve ortak sonuçlara tam anlamıyla ulaşılamamış olmanın nedeni olarak, çalışmalarda kullanılan analiz ve modelleme yöntemlerinin çeşitliliği veya farklılığı öne sürülmüştür. İleride yapılacak olan çalışmalar için genel ve kabul görmüş ortak bir yöntemle daha fazla araştırma yapılması önerilmektedir. Bu derlemede, son zamanlarda miRNA’lar ile yapılan çeşitli çalışmaların farklı yönleriyle ele alınarak özetlenmesi amaçlanmıştır.

Keywords

Vücut sıvıları tanımlanması, mikro RNA, adli bilimler, olay yeri, qPCR.

References

• Çetli E, Tatar D, Özkoçak V. Adli bilimlerde DNA parmak izine adli genetik ve adli antropolojik bakış. Bitlis Eren Üniversitesi Fen Bilimleri Derg. 2019;8(4):1545–56. https://doi.org/10.17798/bitlisfen.537780
• Al-Mawlah YH, Jebor MA, Abdulla AA. The effect of mixing seminal fluid and vaginal secretion on the expression of miRNA markers in a simulated forensic scientific detection. Ann Rom Soc Cell Biol. 2021;25(4):11477–82.
• Alakoç YD. Adli bilimlerde DNA analizleri. Ankara Sağlık Hizmetleri Derg. 2019;9(2):1–8.
• He H, Han N, Ji C, Zhao Y, Hu S, Kong Q, Ye J, Ji A, Sun Q. Identification of five types of forensic body fluids based on stepwise discriminant analysis. Forensic Sci Int Genet. 2020;48:102337. https://doi.org/10.1016/j. fsigen.2020.102337
• Rao A, Rana M, Pradhan A, Sinha M. RNA and DNA based identification of body fluids. Forensic DNA Typing: Principles, Applications and Advancements. 2020;87–104. https://doi.org/10.1007/978-981-15-6655-4_5
• Rhodes C, Lewis C, Szekely J, Campbell A, Creighton MRA, Boone E, Seashols-Williams S. Developmental validation of a microRNA panel using quadratic discriminant analysis for the classification of seven forensically relevant body fluids. Forensic Sci Int Genet. 2022;102692. https://doi.org/10.1016/j.fsigen.2022.102692
• Glynn CL. Potential applications of microRNA profiling to forensic investigations. RNA. 2020;26(1):1–9. https://doi. org/10.1261/rna.072173.119
• Li Z, Lv M, Peng D, Xiao X, Fang Z, Wang Q, Zhang L. Feasibility of using probabilistic methods to analyse microRNA quantitative data in forensically relevant body fluids: a proofof-principle study. Int J Legal Med. 2021;135:2247–61. https://doi.org/10.1007/s00414-021-02678-w
• Hanson EK, Lubenow H, Ballantyne J. Identification of forensically relevant body fluids using a panel of differentially expressed microRNAs. Anal Biochem. 2009;387:303–14. https://doi.org/10.1016/j.ab.2009.01.037
• Han J, Han N, Xu Z, Zhang C, Liu J, Ruan M. Expression profile of circular RNA and construction of circular RNA, Micro RNA network in salivary adenoid cystic carcinoma. Cancer Cell Int. 2021;21(1):1–11. https://doi.org/10.1186/ s12935-020-01681-2
• Menini M, De Giovanni E, Bagnasco F, Delucchi F, Pera F, Baldi D, Pesce P. Salivary micro-RNA and oral squamous cell carcinoma: a systematic review. J Pers Med. 2021;11(2):101. https://doi.org/10.3390/jpm11020101
• Fox AJ. Effects of microwave radiation on the digestion of proteins involved in body fluid identification. NY: The City University of New York; 2020.
• Rocchi A, Chiti E, Maiese A, Turillazzi E, Spinetti I. MicroRNAs: an update of applications in forensic science. Diagnostics. 2020;11.(1):32. https://doi.org/10.3390/diagnostics11010032
• Lewis CA, Layne TR, Seashols‐Williams SJ. Detection of microRNAs in DNA extractions for forensic biological source identification. J Forensic Sci. 2019;64(6):1823–30. https://doi.org/10.1111/1556-4029.14070
• Praihirunkit P. miRNAs: perspective towards the use for body fluid identification. Siriraj Med J. 2020;72(6):512–26. https://doi.org/10.33192/Smj.2020.70
• Xiao Y, Chen D, Peng D, Li Z, Qu S, Zhang R, Liu G, Zheng Y, Mengyu T, Xue J, Zhang Y, Zhu J, Liang W. Establishment of a co-analysis system for personal identification and body fluid identification: a preliminary report. Int J Legal Med. 2022;136(6):1565–75. https://doi.org/10.1007/s00414-022- 02886-y
• Turiello R, Nouwairi RL, Landers JP. Taking the microfluidic approach to nucleic acid analysis in forensics: review and perspectives. Forensic Sci Int Genet. 2023;63:102824. https://doi.org/10.1016/j.fsigen.2022.102824
• Gulyaeva LF, Kushlinskiy NE. Regulatory mechanisms of microRNA expression. J Transl Med. 2016;14(1):143. https://doi.org/10.1186/s12967-016-0893-x
• Lee RC, Feinbaum RL, Ambros V. The C. Elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54. https://doi.org/10.1016/0092-8674(93)90529-Y
• Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 2000;408:86–9. https://doi.org/10.1038/35040556
• Maiese A, Scatena A, Costantino A, Di Paolo M, La Russa R, Turillazzi E, Frati P, Fineschi V. MicroRNAs as useful tools to estimate time since death. a systematic review of current literature. Diagnostics. 2021;11(1):64. https://doi.org/10.3390/diagnostics11010064
• Janjic K, Reisinger C, Kanz F. Common ground between biological rhythms and forensics. Biology. 2022;11(7):1071. https://doi.org/10.3390/biology11071071
• Alshehhi S, Haddrill PR. Evaluating the effect of body fluid mixture on the relative expression ratio of blood-specific RNA markers. Forensic Sci Int. 2020;307:110116. https://doi.org/10.1016/j.forsciint.2019.110116
• Paranjape T, Slack FJ, Weidhaas JB. MicroRNAs: tools for cancer diagnostics. Gut. 2009;58(11):1546–54. https://doi.org/10.1136/gut.2009.179531
• Santonocito S, Polizzi A, Palazzo G, Isola G. The emerging role of microRNA in periodontitis: pathophysiology, clinical potential and future molecular perspectives. Int J Mol Sci. 2021;22(11):5456.https://doi.org/10.3390/ijms22115456
• Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002;21:4663–70. https://doi.org/10.1093/emboj/cdf476
• Shomron N, Levy C. MicroRNA-biogenesis and pre-mRNA splicing crosstalk. Biomed Res Int. 2009;2009:1–6. https://doi.org/10.1155/2009/594678
• Toyama K, Kiyosawa N, Watanabe K, Ishizuka H. Identification of circulating miRNAs differentially regulated by opioid treatment. Int J Mol Sci. 2017;18(9):1991. https://doi.org/10.3390/ijms18091991
• O’Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol (Lausanne). 2018;9:402. https://doi.org/10.3389/fendo.2018.00402
• Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005;123:631–40. https://doi.org/10.1016/j.cell.2005.10.022
• Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11:228–34. https://doi.org/10.1038/ncb0309-228
• Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA. 2003;100:5779–84. https://doi.org/10.1073/pnas.1630797100
• Vaziri PA, Rezaeıeh KAP. Ökaryot Hücrelerde Korunmuş Mikro RNA’lar ve Hedef Transkripsyonların Faliyetleri. Türk Bilimsel Derlemeler Derg. 2012;2:96–8.
• Cerqueira DM, Tayeb M, Ho J. MicroRNAs in kidney development and disease. JCI Insight. 2022;7(9):158277. https://doi.org/10.1172/jci.insight.158277
• Stefani G, Slack FJ. Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol. 2008;9:219–30. https:// doi.org/10.1038/nrm2347
• Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nature Cell Biol. 2005;7:719–23. https://doi.org/10.1038/ncb1274
• Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455:58–63. https://doi.org/10.1038/nature07228
• Güzelgül F, Aksoy K. A gene expression regulator: miRNA. Arşiv Kaynak Tarama Derg. 2015;24(4):472–93. https://doi.org/10.17827/aktd.95263
• Erdal ME, Yılmaz ŞG. mikroRNA çalışmaları ve psikiyatriye yansıması. Turkiye Klinikleri Journal of Psychiatry Special Topics. 2016;9(1):16–24.
• Sidekli Ö, Korkmaz Ağaoğlu Ö. Kantitatif RT-PCR (RTqPCR) ile mikroRNA (miRNA) ekspresyon profillemesi. Erciyes Üniv Vet Fak Derg. 2020;18(1):48–56. https://doi.org/10.32707/ercivet.878031
• Madea B, Saukko P, Oliva A, Musshoff F. Molecular pathology in forensic medicine-Introduction. Forensic Sci Int. 2010;203(1-3):3–14. https://doi.org/10.1016/j.forsciint.2010.07.017
• Çubuk C. Biyoinformatik teknikleri kullanarak yeni mikro RNAların bulunması ve varyant analizlerinin yapılması: Citrus modeli. Dokuz Eylül üniversitesi, İzmir, 2019.
• Dash HR. NGS-based detection and differentiation of forensically relevant body fluids using conventional, molecular, and microbial techniques. In: Al-Snan NR, Elkins KM, editors. Next Generation Sequencing (NGS) Technology in DNA Analysis. India: Academic Press; 2024. p. 425-50. https://doi.org/10.1016/B978-0-323-99144-5.00003-2
• Virkler K, Lednev IK. Analysis of body fluids for forensic purposes: from laboratory testing to non-destructive rapid confirmatory identification at a crime scene. Forensic Sci Int. 2009;188(1-3):1–17. https://doi.org/10.1016/j. forsciint.2009.02.013
• Chen H, Hu S, Yang R, Hu S, Yao Q, Zhao Y, Lian J, Ji A, Cao Y, Sun, Q. The screening and validation process of miR-223-3p for saliva identification. Legal Medicine. 2023;65:102312.
• Wei S, Hu S, Han N, Wang G, Chen H, Yao Q, Zhao Y, Ye J, Ji A, Sun, Q. Screening and evaluation of endogenous reference genes for miRNA expression analysis in forensic body fluid samples. Forensic Sci Int Genet. 2023;63:102827. https://doi.org/10.1016/j.fsigen.2023.102827
• Sirker M, Fimmers R, Schneider PM, Gomes I. Evaluating the forensic application of 19 target microRNAs as biomarkers in body fluid and tissue identification. Forensic Sci Int Genet. 2017;27:41–9. https://doi.org/10.1016/j.fsigen.2016.11.012
• Iroanya OO, Olutunde OT, Egwuatu TF, Igbokwe C. Stability of selected microRNAs in human blood, semen and saliva samples exposed to different environmental conditions. Forensic Sci Int. 2022;336:111338. https://doi.org/10.1016/j.forsciint.2022.111338
• Al-Mawlah YH, Asma’a HM, Abd-Alameer AM, Hadi AM, Abdulabbas HS, Shaheed SH, Jebor MA, Alsaadi AH. Assessment of the specificity and stability of micro RNAs as a forensic gene marker. Biomed Biotechnol Res J. 2023;7(4):569–76. https://doi.org/10.4103/bbrj.bbrj_174_23
• Primorac D, Schanfield M. Forensic body fluid and tissue identification. In: Primorac D, Schanfield M, editors. Forensic DNA applications: An interdisciplinary perspective. Florida: CRC Press, 2023. p. 319-42. https://doi.org/10.4324/9780429019944-18
• Ünal MS, Özer MC, Sönmez FH, Bayrak G, Demirbağ HO. Seminal sıvının fertilizasyondaki rolü. Androl Bul. 2017;19(4):138−43. https://doi.org/10.24898/tandro.2017.35403
• Wen YG, Yu H, Lin JS. Advanced technologies in semen stain identification. Zhonghua Nan Ke Xue. 2016;22(6):553–58.
• Kiani M, Salehi M, Mogheiseh A. MicroRNA expression in infertile men: its alterations and effects. Zygote. 2019;27(5):263–71. https://doi.org/10.1017/S0967199419000340
• Al-Mawlah YH, Al-Darraji MN, Al-Imari MJ. Study of small non-coding RNA (miRNA) expression pattern of fertile/ infertile male semen. Acta Inform Med. 2022;30(3):205. https://doi.org/10.5455/aim.2022.30.205-212
• Lian J, Zhang X, Tian H, Liang N, Wang Y, Liang C, Li X, Sun, F. Altered microRNA expression in patients with non-obstructive azoospermia. Reprod Biol Endocrinol. 2009;7(1):1–10. https://doi.org/10.1186/1477-7827-7-13
• Mokanszki A, Molnar Z, Varga Tothne E, Bodnar B, Jakab A, Balint BL, Balogh I. Altered microRNAs expression levels of sperm and seminal plasma in patients with infertile ejaculates compared with normozoospermic males. Hum Fertil. 2020;23(4):246–55. https://doi.org/10.1080/14647273.2018.1562241
• Keles E, Malama E, Bozukova S, Siuda M, Wyck S, Witschi U, Bauersachs S, Bollwein H. The micro-RNA content of unsorted cryopreserved bovine sperm and its relation to the fertility of sperm after sex-sorting. BMC Genomics. 2021;22:1–19. https://doi.org/10.1186/s12864-020-07280-9
• Joshi M, Andrabi SW, Yadav RK, Sankhwar SN, Gupta G, Rajender S. Qualitative and quantitative assessment of sperm miRNAs identifies hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p as potential biomarkers of male infertility and sperm quality. Reprod Biol Endocrinol. 2022;20(1):122. https://doi.org/10.1186/s12958-022-00990-7
• He H, Ji A, Zhao Y, Han N, Hu S, Kong Q, Jiang L, Ye J, Liu Y, Sun Q. A stepwise strategy to distinguish menstrual blood from peripheral blood by Fisher’s discriminant function. Int J Legal Med. 2020;134:845–51. https://doi.org/10.1007/s00414-019-02196-w
• Wang Z, Luo H, Pan X, Liao M, Hou Y. A model for data analysis of microRNA expression in forensic body fluid identification. Forensic Sci Int Genet. 2012;3:419–23. https://doi.org/10.1016/j.fsigen.2011.08.008
• Qin AY, Zhang XW, Liu L, Yu JP, Li H, Wang SZ, Ren XB, Cao S. MiR-205 in cancer: an angel or a devil. Eur J Cell Biol. 2013;92:54–60. https://doi.org/10.1016/j.ejcb.2012.11.002
• Qiang R, Wang F, Shi LY, Liu M, Chen S, Wan HY, Li YX, Li X, Gao SY, Sun BC, Tang H. Plexin-B1 is a target of miR214 in cervical cancer and promotes the growth and invasion of HeLa cells. Int J Biochem Cell Biol. 2011;43(4):632–41. https://doi.org/10.1016/j.biocel.2011.01.002
• Bexon K, Williams G. Characterising the Fluctuation of MicroRNA Expression throughout a Full Menstrual Cycle. Forensic Sci Int Genet Supplement Series. 2015;5:e264–266. https://doi.org/10.1016/j.fsigss.2015.09.105
• Valentine A. (2021). Differentiation between peripheral blood and menstrual blood using miRNA markers (Unpublished Thesis). Virginia: Virginia Commonwealth University; 2021.
• Wang G, Wang Z, Wei S, Wang D, Ji A, Zhang W, Sun Q. A new strategy for distinguishing menstrual blood from peripheral blood by the miR-451a/miR-21-5p ratio. Forensic Sci Int Genet. 2022;57:102654. https://doi.org/10.1016/j.fsigen.2021.102654
• Ali EM, Edwards HG, Scowen IJ. In-situ detection of single particles of explosive on clothing with confocal Raman microscopy. Talanta. 2009;78(3):1201–03. https://doi.org/10.1016/j.talanta.2008.12.038
• Sakurada K, Watanabe K, Akutsu T. Current methods for body fluid identification related to sexual crime: focusing on saliva, semen, and vaginal fluid. Diagnostics. 2020;10(9):693. https://doi.org/10.3390/diagnostics10090693
• Rhodes C, Lewis C, Price K, Valentine A, Creighton MRA, Boone E, Seashols-Williams, S. Evaluation and verification of a microrna panel using quadratic discriminant analysis for the classification of human body fluids in dna extracts. Genes. 2023;14(5):968. https://doi.org/10.3390/genes14050968
• Li Z, Chen D, Wang Q, Tian H, Tan M, Peng D, Tan Y, Zhu J, Liang W, Zhang L. mRNA and microRNA stability validation of blood samples under different environmental conditions. Forensic Sci Int Genet. 2021;55:102567. https://doi.org/10.1016/j.fsigen.2021.102567
• Liu Y, He H, Xiao ZX, Ji A, Ye J, Sun Q, Cao Y. A systematic analysis of miRNA markers and classification algorithms for forensic body fluid identification. Brief Bioinform. 2021;22(4): bbaa324. https://doi.org/10.1093/bib/bbaa324
• Huang H, Liu X, Cheng J, Xu L, He X, Xiao C, Huang D, Yi S. A novel multiplex assay system based on 10 methylation markers for forensic identification of body fluids. J Forensic Sci. 2022;67(1):136–48. https://doi.org/10.1111/1556-4029.14872
• Dobay A, Haas C, Fucile G, Downey N, Morrison HG, Kratzer A, Arora N. Microbiome-based body fluid identification of samples exposed to indoor conditions, Forensic Sci Int Genet. 2019;40:105–13. https://doi.org/10.1016/j.fsigen.2019.02.010
• Bamberg M, Bruder M, Dierig L, Kunz SN, Schwender M, Wiegand P. Best of both: A simultaneous analysis of mRNA and miRNA markers for body fluid identification. Forensic Sci Int Genet. 2022;59:102707. https://doi.org/10.1016/j.fsigen.2022.102707
• Chen X, Xu H, Zhu B. Forensic validation of a combined analysis of mRNA and miRNA markers for precise tissue origin inferences of five kinds of body fluids by RT‐qPCR. Electrophoresis. 2023;44(21-22):1714–24. https://doi.org/10.1002/elps.202300059
• Liang X, Han X, Liu C, Du W, Zhong P, Huang L, Huang M, Fu L, Liu C, Chen L. Integrating the salivary microbiome in the forensic toolkit by 16S rRNA gene: potential application in body fluid identification and biogeographic inference. Int J Legal Med. 2022;136(4):975–85. https://doi.org/10.1007/s00414-022-02831-z
• Lewis CA, Seashols‐Williams SJ. A combined molecular approach utilizing microbial DNA and microRNAs in a qPCR multiplex for the classification of five forensically relevant body fluids. J Forensic Sci. 2024;69:282–90. https://doi.org/10.1111/1556-4029.15400