Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Clinical Cancer Study Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, China; Department of Gastroenterology, Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Hum Pathol. 2018 Jun;76:58-67. doi: 10.1016/j.humpath.2018.03.011. Epub 2018 Mar 16.
Microrchidia 2 (MORC2) plays important roles in DNA damage repair and lipogenesis, but the clinical and functional role of MORC2 in cancer remains largely unexplored. In this study, we showed that MORC2 was widely expressed in human tissues while significantly up-regulated in most cancer types using immunohistochemical staining and analysis of messenger RNA expression profile of more than 2000 human tissue samples from 15 different organs (lung, prostate, liver, breast, brain, stomach, colon/rectum, pancreas, ovary, endometrium, skin, nasopharynx, kidney, esophagus, and bladder). We also found that the MORC2 expression level in high-grade cancer tissues was much more elevated and associated with unfavorable pathological characteristics, poor overall survival, and disease-free survival in several kinds of cancers such as non-small cell lung cancer and breast cancer. Gene set enrichment analysis was used to predict the genes modulated by MORC2, and the results showed that dysregulation of MORC2 in tumor may take part in the cell cycle regulation and genomic instability. We observed that MORC2 knockdown would arrest the cell cycle progress, and the genome of tumors with high MORC2 expression contained more point mutations and gene copy number variation, which validates our gene set enrichment analysis results. The results also showed that MORC2 knockdown would significantly inhibit the proliferation, colony forming, migration, and invasion in multiple cancer cell lines. Taken together, these results highlight the importance of MORC2 in tumorigenesis and cancer progression, and it may act as a potential diagnostic marker and therapeutic target for these diseases.
微体 2（MORC2）在 DNA 损伤修复和脂肪生成中发挥重要作用，但 MORC2 在癌症中的临床和功能作用在很大程度上仍未得到探索。在这项研究中，我们通过免疫组织化学染色和对来自 15 个不同器官（肺、前列腺、肝、乳腺、脑、胃、结肠/直肠、胰腺、卵巢、子宫内膜、皮肤、鼻咽、肾、食管和膀胱）的 2000 多个人类组织样本的信使 RNA 表达谱进行分析，表明 MORC2 在人类组织中广泛表达，而在大多数癌症类型中则显著上调。我们还发现，高级别癌症组织中的 MORC2 表达水平更高，与多种癌症（如非小细胞肺癌和乳腺癌）中的不良病理特征、总体生存率和无病生存率相关。基因集富集分析用于预测受 MORC2 调节的基因，结果表明，肿瘤中 MORC2 的失调可能参与细胞周期调控和基因组不稳定性。我们观察到 MORC2 敲低会导致细胞周期进程停滞，而高 MORC2 表达的肿瘤基因组包含更多的点突变和基因拷贝数变异，这验证了我们的基因集富集分析结果。结果还表明，MORC2 敲低会显著抑制多种癌细胞系的增殖、集落形成、迁移和侵袭。总之，这些结果强调了 MORC2 在肿瘤发生和癌症进展中的重要性，它可能作为这些疾病的潜在诊断标志物和治疗靶点。
