Loss of Runx1 Induces Granulosa Cell Defects and Development of Ovarian Tumors in the Mouse.
Loss of Runx1 Induces Granulosa Cell Defects and Development of Ovarian Tumors in the Mouse.
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DOI：
10.3390/ijms232214442
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发表时间：
2022-11-21
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
RUNX 1基因的遗传改变与多种恶性肿瘤相关，包括女性相关癌症。RUNX 1作为肿瘤抑制基因或癌基因的作用是组织依赖性的，并且根据癌症类型而变化。RUNX 1基因的扩增和缺失都与人类卵巢癌有关。在这项研究中，我们研究了Runx 1缺失对小鼠卵巢发病机制的影响。卵巢体细胞中Runx 1的条件性缺失导致老年小鼠卵巢肿瘤患病率增加。到15个月大时，27%的Runx 1基因敲除（KO）女性发生了具有颗粒细胞瘤特征的卵巢肿瘤。虽然年轻成年小鼠的卵巢没有显示肿瘤，但它们都含有异常的卵泡样病变。构成这些卵泡样病变的颗粒细胞是静止的，显示分化缺陷，并组织成玫瑰花状图案。RNA测序分析进一步揭示了Runx 1 KO卵巢中差异表达的基因，包括涉及化生、卵巢癌、上皮细胞发育、紧密连接、细胞-细胞粘附和Wnt/β-连环蛋白通路的基因。总之，这项研究表明Runx 1是正常颗粒细胞分化和预防小鼠卵巢肿瘤发展所必需的。
Genetic alterations of the RUNX1 gene are associated with a variety of malignancies, including female-related cancers. The role of RUNX1 as either a tumor suppressor gene or an oncogene is tissue-dependent and varies based on the cancer type. Both the amplification and deletion of the RUNX1 gene have been associated with ovarian cancer in humans. In this study, we investigated the effects of Runx1 loss on ovarian pathogenesis in mice. A conditional loss of Runx1 in the somatic cells of the ovary led to an increased prevalence of ovarian tumors in aged mice. By the age of 15 months, 27% of Runx1 knockout (KO) females developed ovarian tumors that presented characteristics of granulosa cell tumors. While ovaries from young adult mice did not display tumors, they all contained abnormal follicle-like lesions. The granulosa cells composing these follicle-like lesions were quiescent, displayed defects in differentiation and were organized in a rosette-like pattern. The RNA-sequencing analysis further revealed differentially expressed genes in Runx1 KO ovaries, including genes involved in metaplasia, ovarian cancer, epithelial cell development, tight junctions, cell−cell adhesion, and the Wnt/beta-catenin pathway. Together, this study showed that Runx1 is required for normal granulosa cell differentiation and prevention of ovarian tumor development in mice.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
16.6
作者：
Labidi-Galy SI;Papp E;Hallberg D;Niknafs N;Adleff V;Noe M;Bhattacharya R;Novak M;Jones S;Phallen J;Hruban CA;Hirsch MS;Lin DI;Schwartz L;Maire CL;Tille JC;Bowden M;Ayhan A;Wood LD;Scharpf RB;Kurman R;Wang TL;Shih IM;Karchin R;Drapkin R;Velculescu VE
通讯作者：
Velculescu VE
影响因子：
3.5
作者：
Chassot, Anne-Amandine;Ranc, Fariba;Chaboissier, Marie-Christine
通讯作者：
Chaboissier, Marie-Christine
影响因子：
--
作者：
Liu, Zhilin;Ren, Yi A.;Richards, JoAnne S.
通讯作者：
Richards, JoAnne S.
影响因子：
16.6
作者：
Chimge NO;Little GH;Baniwal SK;Adisetiyo H;Xie Y;Zhang T;O'Laughlin A;Liu ZY;Ulrich P;Martin A;Mhawech-Fauceglia P;Ellis MJ;Tripathy D;Groshen S;Liang C;Li Z;Schones DE;Frenkel B
通讯作者：
Frenkel B