Wei Li, Wei Qianfeng, Yang Xiaojun, Zhou Peng
Department of Blood Transfusion, the Third Affiliated Hospital of Soochow University, Changzhou, China.
Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Ann Transl Med. 2022 Feb;10(4):181. doi: 10.21037/atm-21-6894.
Gliomas in the adult brain are complicated and aggressive with a poor prognosis. Gene therapy is a recent alternative glioma treatment. We sought to explore the mechanism of chemokine-like factor (CKLF) MARVEL transmembrane domain-containing 6 (CMTM6) in glioma.
The Cancer Genome Atlas database reports that CMTM6 is expressed in tumors and glioma tissue. CMTM6 expression in glioma tissues and cells was detected and its relationship with clinical pathology was analyzed. Short hairpin ribonucleic acid-CMTM6 lentivirus was transfected into U87 and U251 cells to evaluate malignant glioma cells. Using the biological website (https://string-db.org/cgi/input.pl?Sessionid) and reference retrieval, the pathway that interacted with CMTM6 and related to glioma was identified. The level of the mammalian target of rapamycin pathway-related proteins was detected. Functional rescue experiments were performed using the combination of mTOR activator MHY1485 and the knockdown CMTM6. The growth of xenograft tumors was observed and Ki67-positive expression was determined.
CMTM6 upregulation in gliomas was associated with a poor prognosis. CMTM6 expression was notably higher in gliomas. After the knockdown of CMTM6, the proliferation, invasion, and migration of U87 and U251 cells were inhibited, and the apoptosis rate was increased. Knocking down CMTM6 inactivated the mTOR pathway. The activation of mTOR pathway reversed the inhibitory effects of CMTM6 knockdown on glioma cell behaviors. CMTM6 knockdown reduced tumor volume, body mass, and Ki67-positive expression.
The knockdown of CMTM6 inhibited the activation of mTOR pathway and prevented the malignant episodes of glioma cells.
成人大脑胶质瘤病情复杂且侵袭性强，预后较差。基因治疗是近期一种治疗胶质瘤的替代方法。我们试图探究趋化因子样因子（CKLF）含MARVEL跨膜结构域6（CMTM6）在胶质瘤中的作用机制。
癌症基因组图谱数据库显示CMTM6在肿瘤和胶质瘤组织中表达。检测CMTM6在胶质瘤组织和细胞中的表达，并分析其与临床病理的关系。将短发夹核糖核酸-CMTM6慢病毒转染至U87和U251细胞中，以评估恶性胶质瘤细胞。利用生物网站（https://string-db.org/cgi/input.pl?Sessionid）并检索参考文献，确定与CMTM6相互作用且与胶质瘤相关的信号通路。检测雷帕霉素哺乳动物靶标信号通路相关蛋白的水平。使用mTOR激活剂MHY1485与敲低CMTM6相结合进行功能挽救实验。观察异种移植瘤的生长情况，并测定Ki67阳性表达。
胶质瘤中CMTM6上调与预后不良相关。CMTM6在胶质瘤中的表达明显更高。敲低CMTM6后，U87和U251细胞的增殖、侵袭和迁移受到抑制，凋亡率增加。敲低CMTM6使mTOR信号通路失活。mTOR信号通路的激活逆转了CMTM6敲低对胶质瘤细胞行为的抑制作用。敲低CMTM6可减小肿瘤体积、降低体重并减少Ki67阳性表达。
敲低CMTM6可抑制mTOR信号通路的激活，并阻止胶质瘤细胞的恶性进展。
