基于白细胞介素-6/信号传导及转录激活蛋白3信号通路探讨长链非编码RNA-1614在乳腺癌骨转移中的调控机制

The regulatory mechanism of long non-coding RNA-1614 in breast cancer bone metastasis through interleukin-6/signaling and transcription-activating protein 3 pathway

目的探讨长链非编码RNA(LncRNA)-1614和白细胞介素-6(IL-6)/信号传导及转录激活蛋白3(STAT3)信号传导通路在乳腺癌骨转移患者的表达水平及其在潜在作用机制。方法回顾性分析2021年1月至2023年1月南昌市人民医院收治的25例乳腺癌骨转移患者的临床资料,检测并比较乳腺癌原发病灶肿瘤组织、乳腺癌原发癌癌旁组织、乳腺癌骨转移灶肿瘤组织、乳腺癌骨转移灶癌旁组织中LINC01614和IL-6、STAT3相对表达量,分析LINC01614与IL-6、STAT3相对表达量的相关性。选取SPF级健康雌性小鼠20只,进一步构建乳腺癌骨转移小鼠模型,获取模型小鼠骨转移灶组织作为模型组(n=10),同时,以正常健康小鼠作为对照组(n=10),检测并比较模型组与对照组乳腺癌骨转移肿瘤组织中LINC01614和IL-6、STAT3mRNA相对表达量。结果乳腺癌原发灶、乳腺癌骨转移灶癌组织中LINC01614相对表达量均高于乳腺癌原发灶、乳腺癌骨转移灶癌旁组织,且乳腺癌骨转移灶癌组织高于乳腺癌原发灶癌组织,差异有统计学意义(P<0.05)。乳腺癌骨转移灶癌组织中IL-6、STAT3相对表达量均高于乳腺癌骨转移灶癌旁组织,差异有统计学意义(P<0.05)。乳腺癌骨转移灶癌组织LINC01614相对表达量与IL-6、STAT3相对表达量均呈正相关(r>0,P<0.05)。乳腺癌骨转移模型组小鼠LINC01614及IL-6、STAT3的mRNA相对表达量均高于对照组,差异有统计学意义(P<0.05)。结论LINC01614在乳腺癌骨转移患者中表达水平异常升高,可能具有促进乳腺癌患者骨转移的作用,其作用机制可能与IL-6/STAT3信号传导通路的激活有关。

Objective To investigate the expression of long non-coding RNA(LncRNA)-1614(LINC01614)and interleukin-6(IL-6)/signaling and transcription-activating protein 3(STAT3)pathway in breast cancer patients with bone metastasis and their potential mechanisms of action.Methods The clinical data of 25 breast cancer patients with bone metastases admitted to Nanchang People's Hospital from January 2021 to January 2023 were retrospectively analyzed,the relative expression levels of LINC01614,IL-6 and STAT3 in tumor tissue of primary breast cancer,adjacent tissues of primary breast cancer,bone metastases of breast cancer and adjacent tissues of bone metastases of breast cancer were detected and com-pared,and the correlation between LINC01614 and relative expression levels of IL-6 and STAT3 was analyzed.Twenty healthy female mice with SPF grade were selected to further construct the breast cancer bone metastasis mouse model,and the bone metastasis tissue of model mice was ob-tained as the model group(n=10),and normal healthy mice were used as the control group(n=10),the mRNA expression levels of LINC01614,IL-6 and STAT3 in bone metastases of breast cancer were detected and compared between the model group and the control group.Results The relative expression level of LINC01614 in the tumor tissues of primary breast cancer and bone metastatic breast cancer were higher than that in the adjacent tissues of primary breast cancer and bone metastatic breast cancer,and the tumor tissues of bone metastatic breast cancer were higher than that in the tumor tissues of primary breast cancer,the differences were statistically significant(P<0.05).The relative expression levels of IL-6 and STAT3 in the tumor tissues of breast cancer with bone metastasis were higher than those in the adjacent tissues of breast cancer bone metastases,and the differ-ence was statistically significant(P<0.05).The relative expression levels of LINC01614 were positively correlated with the relative expression of IL-6 and STAT3 in the tumor tissues of bone metastases of breast cancer(r>0,P<0.05).The mRNA relative expression levels of LINC01614,IL-6 and STAT3 in the breast cancer bone metastasis model group were higher than those in the control group,difference was statistically significant(P<0.05).Conclusion The expression level of LINC01614 is abnormally increase in breast cancer patients with bone metastasis,which could promote bone metastasis in breast cancer patients,and the mechanism may be related to the activation of IL-6/STAT3 signaling pathway.