Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma.
Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma.
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DOI：
10.3390/cancers13225623
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发表时间：
2021-11-10
期刊：
影响因子：
5.2
通讯作者：
Wang CI
中科院分区：
文献类型：
--
作者：
Chen TW;Chang KP;Cheng CC;Chen CY;Hong SW;Sie ZL;Cheng HW;Yen WC;Huang Y;Liu SC;Wang CI
放射抵抗是口腔鳞癌放射治疗失败的主要原因之一。通过系统比较TCGA-OSCC患者放疗前后所有基因的预后价值，确定放射抵抗相关基因。研究发现，只有在TCGA和另一个独立的台湾队列中接受放射治疗的口腔鳞癌患者中，RPL36A转录水平较高与预后不良相关。RPL36A后来被证明参与了DNA损伤、细胞周期和细胞凋亡的调节，导致了辐射抗性。因此，这样的综合研究有望为未来放射抵抗口腔鳞癌的新的治疗干预措施的发展带来极大的好处。放射抵抗是口腔鳞癌放射治疗失败的主要原因之一。通过比较肿瘤基因组图谱(TCGA)-口腔鳞癌队列中表达的20,502个基因的预后价值，发现297个基因与接受放射治疗的口腔鳞癌患者的无病生存率差呈正相关，这些基因是潜在的放射抵抗相关基因。在潜在的辐射抗性相关基因中，36个基因在癌组织中相对于正常组织表达上调。生物信息学分析表明，60S核糖体蛋白L36A(RPL36A)是辐射抗性相关基因介导的生物学途径中最常见的检测基因。然后，对两个独立的队列(n=162和n=136)进行评估，以证实只有在接受放射治疗的口腔鳞癌患者中，RPL36A转录水平较高与预后不良显著相关。从机制上讲，我们发现RPL36A的敲除通过增加细胞对DNA损伤的敏感性，促进G2/M期细胞周期停滞，进而增强辐射诱导的口腔鳞状细胞癌细胞的凋亡途径，从而增加放射敏感性。综上所述，我们的研究支持使用大规模基因组数据来识别特定的辐射抵抗相关基因，并提示RPL36A在口腔鳞癌放射抵抗发展中的调节作用。
Radioresistance is one of the major factors contributing to radiotherapy failure in OSCC. By systematically comparing the prognostic values of all genes in TCGA-OSCC patients with and without radiotherapy, radioresistance-associated genes were identified. Higher RPL36A transcript levels were found to be associated with a poor prognosis only in OSCC patients with radiotherapy in the cohort of TCGA and another independent Taiwanese cohort. RPL36A was then shown to be involved in the regulation of DNA damage, cell cycle and apoptosis, leading to radioresistance. Thus, such integrated studies are expected to be greatly beneficial for the development of new therapeutic interventions for radioresistant OSCC in the future. Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC.
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影响因子：
--
作者：
Li YL;Chang JT;Lee LY;Fan KH;Lu YC;Li YC;Chiang CH;You GR;Chen HY;Cheng AJ
通讯作者：
Cheng AJ
DOI：
10.3390/curroncol28040213
发表时间：
2021-06-23
期刊：
Current oncology (Toronto, Ont.)
影响因子：
--
作者：
Bennardo L;Bennardo F;Giudice A;Passante M;Dastoli S;Morrone P;Provenzano E;Patruno C;Nisticò SP
通讯作者：
Nisticò SP
影响因子：
15.9
作者：
Li, Ming-Yang;Fan, Lin-Ni;Wang, Zhe
通讯作者：
Wang, Zhe
影响因子：
2.9
作者：
Kudo I;Esumi M;Kusumi Y;Furusaka T;Oshima T
通讯作者：
Oshima T
DOI：
10.1186/1748-717x-6-136
发表时间：
2011-10-12
期刊：
Radiation oncology (London, England)
影响因子：
--
作者：
Lin CY;Lin TY;Wang HM;Huang SF;Fan KH;Liao CT;Chen IH;Lee LY;Li YL;Chen YJ;Cheng AJ;Chang JT
通讯作者：
Chang JT