Department of Gynecologic Oncology, Shandong Tumor Hospital and Institute, Jinan, Shandong Province, China.
Department of Oncology, People's Hospital of Tengzhou City, Shandong, China.
J Cell Biochem. 2018 Jul;119(7):5135-5142. doi: 10.1002/jcb.26488. Epub 2018 Apr 6.
Ovarian cancer is one of the leading gynecologic malignancies globally, the 5-year survival rate for patients with advanced stage ovarian cancer is very low. Our objective was to test the hypothesis that miR-335 was associated with the survival of patients with ovarian cancer. Bioinformatics tools and luciferase report assay were used to select the target of miR-335, and real-time PCR was used to detect the expression of miR-335 and ERBB4 in different genotype groups. Finally, Cox regression and Kaplan-Meier analyses were used to assess the relationship of ERBB4 genotype and survival of ovary cancer. Firstly, individuals carried ERBB4 rs186724 GG genotype had poorer overall survival compared with those carried CC/CT genotypes in ovarian cancer, while the participants with rs1836724 GA genotype had the same overall survival with that in participants with rs1836724 AA genotype in accordance with the result of Cox regression and Kaplan-Meier analyses. Then according to result of the in-silicon analysis, ERBB4 was the target of miR-335, and rs1836724 was located on 3'UTR of ERBB4, the binding site of miR-335, and miR-335 inhibited the expression of ERBB4 and this regulation was more suppressed when the G allele replaced by the variant A allele. Finally, miR-335 was similar among GG, GA, and AA groups, and ERBB4 level was higher in GG group. Finally, malignant grade is apparently higher in GG group than the other group. The data indicated that the ERBB4 rs1836724 polymorphism was associated with the survival of ovarian cancer.
卵巢癌是全球主要的妇科恶性肿瘤之一，晚期卵巢癌患者的 5 年生存率非常低。我们的目的是检验 miR-335 与卵巢癌患者生存相关的假设。使用生物信息学工具和荧光素酶报告实验来选择 miR-335 的靶基因，并用实时 PCR 检测不同基因型组中 miR-335 和 ERBB4 的表达。最后，使用 Cox 回归和 Kaplan-Meier 分析评估 ERBB4 基因型与卵巢癌患者生存的关系。首先，与携带 CC/CT 基因型的个体相比，携带 ERBB4 rs186724 GG 基因型的个体在卵巢癌中总体生存率较差，而携带 rs1836724 GA 基因型的个体与携带 rs1836724 AA 基因型的个体总体生存率相同，这与 Cox 回归和 Kaplan-Meier 分析的结果一致。然后，根据计算机分析的结果，ERBB4 是 miR-335 的靶基因，rs1836724 位于 ERBB4 的 3'UTR 上，是 miR-335 的结合位点，miR-335 抑制 ERBB4 的表达，当 G 等位基因被变异 A 等位基因取代时，这种调节作用受到更多抑制。最后，miR-335 在 GG、GA 和 AA 组之间相似，而 ERBB4 水平在 GG 组中更高。最后，GG 组的恶性程度明显高于其他组。数据表明，ERBB4 rs1836724 多态性与卵巢癌的生存相关。
