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ZIC2 通过 Wnt/β-catenin 通路促进胃癌的生长和干性。

ZIC2 accelerates growth and stemness in gastric cancer through the Wnt/β-catenin pathway.

机构信息

Department of Clinical Laboratory, Jingjiang People's Hospital, Jingjiang, Jiangsu, 214500, China.

Department of General Surgery, Jingjiang People's Hospital, Jingjiang, Jiangsu, 214500, China.

出版信息

Tissue Cell. 2023 Dec;85:102222. doi: 10.1016/j.tice.2023.102222. Epub 2023 Sep 19.

Abstract

In the digestive system, gastric cancer (GC) is one of the most usual pernicious tumors. Despite great improvement has been created in treatment, it is still the second major reason of cancer-relevant death. Thus, further researches are required to explicate the latent molecular mechanisms and look for novel biomarkers. ZIC2 has been confirmed to be a facilitator in diversified cancers. However, the particular regulatory of ZIC2 in GC needs further investigation. In this work, it was notarized that ZIC2 expression was up-regulated in GC, and ZIC2 knockdown weakened GC cell proliferation. Moreover, ZIC2 suppression retarded cell migration and invasion. Additionally, results from the spheroid formation assay and western blot revealed that ZIC2 silencing reduced cell stemness. Next, we discovered that ZIC2 inhibition restrain the Wnt/β-catenin pathway through modulating β-catenin, Axin, c-myc and MMP-7 expression. At last, it was uncovered that ZIC2 repression relieved tumor growth in vivo. In summary, ZIC2 served as a promotive regulator in GC, aggravating growth and stemness in GC progression through the Wnt/β-catenin pathway. This discovery hinted that ZIC2 may be a valid target for anticancer treatment.

摘要

在消化系统中,胃癌(GC)是最常见的恶性肿瘤之一。尽管在治疗方面取得了很大的进展,但它仍然是癌症相关死亡的第二大主要原因。因此,需要进一步研究来阐明潜在的分子机制并寻找新的生物标志物。ZIC2 已被证实是多种癌症的促进因子。然而,ZIC2 在 GC 中的特定调节作用需要进一步研究。在这项工作中,我们证实 ZIC2 在 GC 中表达上调,ZIC2 敲低削弱了 GC 细胞的增殖。此外,ZIC2 抑制抑制了细胞迁移和侵袭。此外,球体形成实验和 Western blot 的结果表明,ZIC2 沉默降低了细胞干性。接下来,我们发现 ZIC2 抑制通过调节β-catenin、Axin、c-myc 和 MMP-7 的表达来抑制 Wnt/β-catenin 通路。最后,我们发现 ZIC2 抑制在体内减轻了肿瘤的生长。总之,ZIC2 作为 GC 的促进调节剂,通过 Wnt/β-catenin 通路加重 GC 进展中的生长和干性。这一发现暗示 ZIC2 可能是癌症治疗的有效靶点。

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