National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, College of Pharmacy, Chongqing University of Arts and Sciences, Chongqing 402160, China.
College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China.
Molecules. 2022 Sep 22;27(19):6247. doi: 10.3390/molecules27196247.
(1) Background: Colorectal cancer (CRC) is a common gastrointestinal malignancy, accounting for the second largest gastrointestinal tumor. MORC2, a newly discovered chromatin remodeling protein, plays an important role in the biological processes of various cancers. However, the potential mechanistic role of MORC2 in promoting proliferation of CRC carcinoma remains unclear. (2) Methods: The Cancer Genome Atlas database was analyzed using bioinformatics to obtain gene expression and clinical prognosis data. The cell proliferation was assessed by CCK8 and EdU assays, as well as xenograft. SA-beta-gal staining, Western blot, and ELISA assay were using to assess the cell senescence and potential mechanism. (3) Results: Our data showed that MORC2 expression was elevated in CRC patients. Depletion of MORC2 inhibited cellular proliferation both in vivo and in vitro. Further studies showed that the depletion of MORC2 enhanced p21 and p53 expression through decreasing HDAC4 and increasing pro-inflammatory factors IL-6 and IL-8, thus, promoting cellular senescence. (4) Conclusions: We concluded that increased MORC2 expression in CRC might play a critical role in tumorigenesis by regulating the cellular senescence, in addition, MORC2 could be a novel biomarker for clinical outcomes and prognosis and a treatment target for CRC.
（1）背景：结直肠癌（CRC）是一种常见的胃肠道恶性肿瘤，占胃肠道肿瘤的第二位。MORC2 是一种新发现的染色质重塑蛋白，在各种癌症的生物学过程中发挥着重要作用。然而，MORC2 在促进 CRC 癌增殖中的潜在机制作用尚不清楚。
（2）方法：利用生物信息学分析癌症基因组图谱数据库，获得基因表达和临床预后数据。通过 CCK8 和 EdU 检测以及异种移植来评估细胞增殖。使用 SA-β-gal 染色、Western blot 和 ELISA 检测来评估细胞衰老和潜在机制。
（3）结果：我们的数据表明，MORC2 在 CRC 患者中的表达上调。MORC2 耗竭抑制体内和体外的细胞增殖。进一步的研究表明，MORC2 通过减少 HDAC4 和增加促炎因子 IL-6 和 IL-8，从而促进细胞衰老，来降低 p21 和 p53 的表达。
（4）结论：我们得出结论，CRC 中 MORC2 的表达增加可能通过调节细胞衰老在肿瘤发生中起关键作用，此外，MORC2 可以作为 CRC 临床结局和预后的新型生物标志物和治疗靶点。
