Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype.
Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype.
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DOI：
10.1172/jci155931
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发表时间：
2022-08-15
影响因子：
15.9
通讯作者：
Ting, David T.
中科院分区：
文献类型：
--
作者：
Porter, Rebecca L.;Sun, Siyu;Flores, Micayla N.;Berzolla, Emily;You, Eunae;Phillips, Ildiko E.;Neelima, K. C.;Desai, Niyati;Tai, Eric C.;Szabolcs, Annamaria;Lang, Evan R.;Pankaj, Amaya;Raabe, Michael J.;Thapar, Vishal;Xu, Katherine H.;Nieman, Linda T.;Rabe, Daniel C.;Kolin, David L.;Stover, Elizabeth H.;Pepin, David;Stott, Shannon L.;Deshpande, Vikram;Liu, Joyce F.;Solovyov, Alexander;Matulonis, Ursula A.;Greenbaum, Benjamin D.;Ting, David T.
病毒样重复元素的异常表达是上皮癌的一个常见特征，重复物种的大量多样性可对癌症转录组进行独特的视野。高度与上皮 - 间质转变（EMT）以及与IFN响应基因的反应，表明SATII的表达更为侵略性，及其与EMT的相关性和与IFN-RESPONSE基因的相关性 - 在卵巢癌RNA-SESEQ数据中也与Shorter carlial corhartiral corhartiral corhartial corhiration of Shore corhiration of shore shore shore shore of of of of shore shore shore shore shorn of of。能够刺激单核细胞衍生的巨噬细胞的细胞外蔬菜表明，通过这些病毒样序列靶向肿瘤微环境，用反义锁定的锁定核酸靶向HSATI，从而刺激了IFN的反应并刺激MHC I在卵巢癌中的表达，从而使卵巢癌的cyr犬在潜在的策略中造成了重复的策略。
Aberrant expression of viral-like repeat elements is a common feature of epithelial cancers, and the substantial diversity of repeat species provides a distinct view of the cancer transcriptome. Repeatome profiling across ovarian, pancreatic, and colorectal cell lines identifies distinct clustering independent of tissue origin that is seen with coding gene analysis. Deeper analysis of ovarian cancer cell lines demonstrated that human satellite II (HSATII) satellite repeat expression was highly associated with epithelial-mesenchymal transition (EMT) and anticorrelated with IFN-response genes indicative of a more aggressive phenotype. SATII expression — and its correlation with EMT and anticorrelation with IFN-response genes — was also found in ovarian cancer RNA-Seq data and was associated with significantly shorter survival in a second independent cohort of patients with ovarian cancer. Repeat RNAs were enriched in tumor-derived extracellular vesicles capable of stimulating monocyte-derived macrophages, demonstrating a mechanism that alters the tumor microenvironment with these viral-like sequences. Targeting of HSATII with antisense locked nucleic acids stimulated IFN response and induced MHC I expression in ovarian cancer cell lines, highlighting a potential strategy of modulating the repeatome to reestablish antitumor cell immune surveillance.