Период обученияСтрана, городУчебное заведениеДополнительная информация
2008–2013 Россия, Москва МГУ им. М.В.Ломоносова, биологический факультет,кафедра биоорганический химии Диплом по специальности биохимия

Гранты и проекты

ПериодДополнительная информация
2014–2016 Участник гранта РФФИ 14-04-32314 мол_а "Исследование функциональной роли коротких изоформ белка PIWIL2 в образовании и поддержании герминогенных опухолей"
2016–2017 Руководитель гранта РФФИ 16-34-01193 мол_а "Роль изоформ белка PIWIL2 в регуляции пролиферации и апоптоза."

Избранные публикации

  1. Gainetdinov I.V., Skvortsova Y.V., Kondratieva S.A., Klimov A., Tryakin A.A., Azhikina T.L. (2018). Assessment of piRNA biogenesis and function in testicular germ cell tumors and their precursor germ cell neoplasia in situ. BMC Cancer 18 (1), 20 [+]

    Aberrant overexpression of PIWI/piRNA pathway proteins is shown for many types of tumors. Interestingly, these proteins are downregulated in testicular germ cell tumors (TGCTs) compared to normal testis tissues. Here, we used germline and TGCT markers to assess the piRNA biogenesis and function in TGCTs and their precursor germ cell neoplasia in situ (GCNIS).

  2. Gainetdinov I., Skvortsova Y., Kondratieva S., Funikov S., Azhikina T. (2017). Two modes of targeting transposable elements by piRNA pathway in human testis. RNA 23 (11), 1614–1625 [+]

    PIWI proteins and their partner small RNAs, termed piRNAs, are known to control transposable elements (TEs) in the germline. Here, we provide evidence that in humans this control is exerted in two different modes. On the one hand, production of piRNAs specifically targeting evolutionarily youngest TEs (L1HS, L1PA2-L1PA6, LTR12C, SVA) is present both at prenatal and postnatal stages of spermatogenesis and is performed without involvement of piRNA clusters. On the other hand, at postnatal stages, piRNAs deriving from pachytene clusters target "older" TEs and thus complement cluster-independent piRNA production to achieve relevant targeting of virtually all TEs expressed in postnatal testis. We also find that converging transcription of antisense-oriented genes contributes to the origin of genic postnatal prepachytene clusters. Finally, while a fraction of pachytene piRNAs was previously shown to arise from long intergenic noncoding RNAs (lincRNAs, i.e., pachytene piRNA cluster primary transcripts), we ascertain that these are a specific set of lincRNAs that both possess distinguishing epigenetic features and are expressed exclusively in testis.

  3. Gainetdinov I.V., Kondratieva S.A., Skvortsova Y.V., Zinovyeva M.V., Stukacheva E.A., Klimov A., Tryakin A.A., Azhikina T.L. (2016). Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas. Oncotarget , [+]

    PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from studying only normal testis and TGCT samples, we also analyzed an intermediate stage, i.e. preneoplastic testis tissues adjacent to TGCTs. Importantly, in this study, we minimized the contribution of patient-to-patient heterogeneity by using matched preneoplastic/TGCT samples. Surprisingly, expression of germ cell marker DDX4 suggests that spermatogenesis is retained in premalignant testis tissues adjacent to nonseminoma, but not those adjacent to seminoma. Moreover, this pattern is followed by expression of PIWI pathway genes, which impacts one of their functions: DNA methylation level over LINE-1 promoters is higher in preneoplastic testis tissues adjacent to nonseminomas than those adjacent to seminomas. This finding might imply distinct routes for development of the two types of TGCTs and could be used as a novel diagnostic marker, possibly, noninvasively. Finally, we studied the role of CpG island methylation in expression of PIWI genes in patient samples and using in vitro experiments in cell line models: a more complex interrelation between DNA methylation and expression of the corresponding genes was revealed.

  4. Skvortsova Y.V., Kondratieva S.A., Zinovyeva M.V., Nikolaev L.G., Azhikina T.L., Gainetdinov I.V. (2016). Intragenic Locus in Human PIWIL2 Gene Shares Promoter and Enhancer Functions. PLoS ONE 11 (6), e0156454 [+]

    Recently, more evidence supporting common nature of promoters and enhancers has been accumulated. In this work, we present data on chromatin modifications and non-polyadenylated transcription characteristic for enhancers as well as results of in vitro luciferase reporter assays suggesting that PIWIL2 alternative promoter in exon 7 also functions as an enhancer for gene PHYHIP located 60Kb upstream. This finding of an intragenic enhancer serving as a promoter for a shorter protein isoform implies broader impact on understanding enhancer-promoter networks in regulation of gene expression.

  5. Gainetdinov I.V., Skvortsova Y.V., Stukacheva E.A., Bychenko O.S., Kondratieva S.A., Zinovieva M.V., Azhikina T.L. (2014). Expression Profiles of PIWIL2 Short Isoforms Differ in Testicular Germ Cell Tumors of Various Differentiation Subtypes. PLoS ONE 9 (11), e112528 [+]

    PIWI family proteins have recently emerged as essential contributors in numerous biological processes including germ cell development, stem cell maintenance and epigenetic reprogramming. Expression of some of the family members has been shown to be elevated in tumors. In particular, PIWIL2 has been probed as a potential neoplasia biomarker in many cancers in humans. Previously, PIWIL2 was shown to be expressed in most tumours as a set of its shorter isoforms. In this work, we demonstrated the presence of its 60 kDa (PL2L60A) and 80 kDa (PL2L80A) isoforms in testicular cancer cell lines. We also ascertained the transcriptional boundaries of mRNAs and alternative promoter regions for these PIWIL2 isoforms. Further, we probed a range of testicular germ cell tumor (TGCT) samples and found PIWIL2 to be predominantly expressed as PL2L60A in most of them. Importantly, the levels of both PL2L60A mRNA and protein products were found to vary depending on the differentiation subtype of TGCTs, i.e., PL2L60A expression is significantly higher in undifferentiated seminomas and appears to be substantially decreased in mixed and nonseminomatous TGCTs. The higher level of PL2L60A expression in undifferentiated TGCTs was further validated in the model system of retinoic acid induced differentiation in NT2/D1 cell line. Therefore, both PL2L60A mRNA and protein abundance could serve as an additional marker distinguishing between seminomas and nonseminomatous tumors with different prognosis and therapy approaches.