Chromodomain Helicase DNA-Binding Protein 5 Inhibits Renal Cell Carcinoma Tumorigenesis by Activation of the p53 and RB Pathways.
Chromodomain Helicase DNA-Binding Protein 5 Inhibits Renal Cell Carcinoma Tumorigenesis by Activation of the p53 and RB Pathways.
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染色质结构域解旋酶 DNA 结合蛋白 5 通过激活 p53 和 RB 途径抑制肾细胞癌肿瘤发生
DOI：
10.1155/2020/5425612
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发表时间：
2020
影响因子：
--
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Huang S;Yan Q;Xiong S;Peng Y;Zhao R;Liu C
染色体结构域解旋酶DNA结合蛋白5（Chromodomain helicase DNA-binding protein 5，CHD 5）在多种肿瘤中发挥重要的抑癌作用。在这项研究中，我们研究了其临床意义和肿瘤发生的分子机制。最初，在原发性肿瘤组织和组织阵列中评估CHD 5表达。分析CHD 5表达与临床病理特征的相关性。接下来，使用慢病毒介导的CHD 5在ACHN和769-P细胞中的过表达来评估对增殖、迁移、侵袭能力以及p14 ARF/p53和p16 INK 4a/RB信号传导途径的调节的影响。最后，使用异种移植小鼠模型来验证其对体内肿瘤生长的影响。结果表明，CHD 5在肿瘤组织中表达下调，并且CHD 5低表达与TNM分期、高Fuhrman分级、淋巴结转移和低生存率相关。CHD 5的过表达在体外抑制增殖、迁移和侵袭;促使细胞周期G1期阻滞;诱导凋亡;并在体内抑制肿瘤生长。此外，我们证实CHD 5激活p53和RB通路以抑制RCC中的肿瘤发生。综上所述，CHD 5参与了RCC的发生和发展，并可能作为RCC的诊断生物标志物和潜在的治疗靶点。
Chromodomain helicase DNA-binding protein 5 (CHD5) plays a crucial tumor suppressor role in multiple types of tumors. For this study, we investigated its clinical significance and the molecular mechanism(s) underlying tumorigenesis in renal cell carcinoma (RCC). Initially, CHD5 expression was assessed in primary tumor tissue and in tissue array. Correlations among CHD5 expression and clinicopathological characteristics were analyzed. Next, lentivirus-mediated CHD5 overexpression in the ACHN and 769-P cells was used to assess effects on proliferation, migration, invasion ability, and the regulation of the p14ARF/p53 and p16INK4a/RB signaling pathways. Finally, a xenograft mouse model was used to verify its impact on tumor growth in vivo. Results demonstrated that CHD5 was downregulated in tumor tissues and that low CHD5 expression was correlated with advanced TNM stage, high Fuhrman grade, lymph node metastasis, and poor survival. Overexpression of CHD5 inhibited proliferation, migration, and invasion in vitro; prompted cell cycle G1 phase arrest; induced apoptosis; and suppressed tumor growth in vivo. Furthermore, we confirmed that CHD5 activates the p53 and RB pathways to inhibit tumorigenesis in RCC. In summary, CHD5 is involved in the initiation and progression of RCC and may serve as a diagnostic biomarker and a potential therapeutic target for RCC.
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影响因子：
37.3
作者：
Garcia I;Mayol G;Rodríguez E;Suñol M;Gershon TR;Ríos J;Cheung NK;Kieran MW;George RE;Perez-Atayde AR;Casala C;Galván P;de Torres C;Mora J;Lavarino C
通讯作者：
Lavarino C
影响因子：
64.8
作者：
Konermann S;Brigham MD;Trevino AE;Joung J;Abudayyeh OO;Barcena C;Hsu PD;Habib N;Gootenberg JS;Nishimasu H;Nureki O;Zhang F
通讯作者：
Zhang F
影响因子：
3.5
作者：
Baykara, Onur;Tansarikaya, Merve;Buyru, Nur
通讯作者：
Buyru, Nur
影响因子：
64.5
作者：
Bagchi, Anindya;Papazoglu, Cristian;Mills, Alea A.
通讯作者：
Mills, Alea A.
影响因子：
64.8
作者：
Berger, Michael F.;Lawrence, Michael S.;Demichelis, Francesca;Drier, Yotam;Cibulskis, Kristian;Sivachenko, Andrey Y.;Sboner, Andrea;Esgueva, Raquel;Pflueger, Dorothee;Sougnez, Carrie;Onofrio, Robert;Carter, Scott L.;Park, Kyung;Habegger, Lukas;Ambrogio, Lauren;Fennell, Timothy;Parkin, Melissa;Saksena, Gordon;Voet, Douglas;Ramos, Alex H.;Pugh, Trevor J.;Wilkinson, Jane;Fisher, Sheila;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Simons, Jonathan W.;Kitabayashi, Naoki;MacDonald, Theresa Y.;Kantoff, Philip W.;Chin, Lynda;Gabriel, Stacey B.;Gerstein, Mark B.;Golub, Todd R.;Meyerson, Matthew;Tewari, Ashutosh;Lander, Eric S.;Getz, Gad;Rubin, Mark A.;Garraway, Levi A.
通讯作者：
Garraway, Levi A.