Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression.

Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression.
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DOI:
10.3390/cancers13143513
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发表时间:
2021-07-14
期刊:
影响因子:
5.2
通讯作者:
Soares MA
Soares MA
中科院分区:
医学2区
文献类型:
--
作者:
Curty G;Menezes AN;Brant AC;de Mulder Rougvie M;Moreira MÂM;Soares MA

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逆转录元件是存在于人类基因组中的内源性DNA元件。它们在肿瘤发生和癌症进展中起关键作用。一些研究已经报道了它们的表达作为癌症的生物标志物和免疫靶点。它们的表达可以通过表观遗传改变和病毒感染来诱导。在不同类型的癌症,如乳腺癌、黑色素瘤、肾细胞癌和前列腺癌中已经显示出逆转录因子过表达。然而,对其他特定类型的癌症,如宫颈癌的研究很少。在这里,我们探讨了宫颈癌中逆转录因子的表达,以及它们与HPV感染的相互作用和它们与邻近基因表达的关联。我们发现宫颈癌特异性逆转录因子的表达与肿瘤组织学类型和HPV感染相关,可作为生物标志物和免疫治疗方法的新靶点。逆转录因子在不同类型的癌症中表达,并且与肿瘤发生和癌症进展相关。我们描述了宫颈癌中逆转录因子的表达,并探讨了它们与HPV感染的相互作用及其与邻近基因表达的相关性。选择40例HPV基因分型的浸润性宫颈癌(鳞状细胞癌和腺癌)活检组织,并通过RNA-seq数据分析人内源性逆转录病毒(HERV)和长散布核元件1(L1)表达。我们发现8060 retroelements中表达的样品和DNA甲基转移酶1的表达与两个最表达的L1元件呈负相关。共发现103个逆转录因子在肿瘤组织学类型和HPV类型之间差异表达,包括几个HERV家族(HERV-K、HERV-H、HERV-E、HERV-I和HERV-L)。HPV单一感染和合并感染之间的比较显示差异表达的L1元件的比例最高。逆转录元件的位置影响相邻基因的表达,如白细胞介素-20基因家族。3个HERV和7个L1位于该基因家族附近,2个L1与IL 20 RB表达呈正相关。本研究描述了宫颈癌中逆转录因子的表达,并显示了它们与HPV状态和宿主基因表达的相关性。
Retroelements are endogenous DNA elements present in the human genome. They have a key role in tumorigenesis and cancer progression. Several studies have reported their expression as biomarkers and immunotherapeutic targets to cancer. Their expression can be induced by epigenetic alteration and virus infections. Retroelement overexpression has been shown in distinct types of cancer, such as breast cancer, melanoma, renal cell carcinoma and prostate cancer. However, studies on other specific types of cancer, such as in cervical cancer, are scarce. Here we explored the expression of retroelements in cervical cancer as well as their interplay with HPV infection and their association with expression of neighboring genes. We find expression of retroelements specific to cervical cancer, associated with tumor histological type and HPV infection, as a new target as biomarkers and for immune therapy approaches. Retroelements are expressed in diverse types of cancer and are related to tumorigenesis and to cancer progression. We characterized the expression of retroelements in cervical cancer and explored their interplay with HPV infection and their association with expression of neighboring genes. Forty biopsies of invasive cervical carcinoma (squamous cell carcinomas and adenocarcinomas) with genotyped HPV were selected and analyzed for human endogenous retrovirus (HERV) and long interspersed nuclear element 1 (L1) expression through RNA-seq data. We found 8060 retroelements expressed in the samples and a negative correlation of DNA methyltransferase 1 expression with the two most expressed L1 elements. A total of 103 retroelements were found differentially expressed between tumor histological types and between HPV types, including several HERV families (HERV-K, HERV-H, HERV-E, HERV-I and HERV-L). The comparison between HPV mono- and co-infections showed the highest proportion of differentially expressed L1 elements. The location of retroelements affected neighboring gene expression, such as shown for the interleukin-20 gene family. Three HERVs and seven L1 were located close to this gene family and two L1 showed a positive association with IL20RB expression. This study describes the expression of retroelements in cervical cancer and shows their association with HPV status and host gene expression.
DOI: 10.1186/s13100-016-0080-x
发表时间: 2016
期刊: Mobile DNA
影响因子: 4.9
作者:
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发表时间: 2010-11-01
期刊: LANCET ONCOLOGY
影响因子: 51.1
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影响因子: --
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发表时间: 2012-03-04
期刊: NATURE METHODS
影响因子: 48
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DOI: 10.3390/v9060130
发表时间: 2017-05-31
期刊: Viruses
影响因子: --
作者:
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通讯作者: Magiorkinis G