泛素样蛋白UBQLN2通过抑制结肠癌Wnt信号通路发挥抑癌作用

Ubiquitin-like Protein UBQLN2 Exerts Tumor Suppressor Effect by Inhibiting Activation of Wnt Signaling Pathway in Colon Cancer

结肠癌是一种危害人类健康的消化道肿瘤,结肠癌复杂的发病机制导致患者治疗效果不佳。泛素样蛋白质2(ubiquilin,UBQLN2)是泛素样蛋白质家族成员之一,参与调控细胞内蛋白质泛素化降解、内质网应激和溶酶体稳态,但是,其在结肠癌中的作用和机制目前尚不清楚。本研究旨在分析UBQLN2在结肠癌中的作用及其与经典促癌Wnt信号通路之间的关系。免疫组化和Western印迹分析结果显示,UBQLN2在结肠癌组织和细胞中表达下调(P<0.05),UBQLN2与结肠癌转移以及临床分期呈显著负相关关系(P<0.05)。CCK-8和流式细胞术检测结果显示,抑制UBQLN2可促进结肠癌细胞增殖,抑制细胞凋亡(P<0.05)。免疫荧光和Western印迹结果显示,抑制UBQLN2可促进Bcl-2,抑制Bax表达,激活Wnt信号通路(P<0.05)。综上所述,泛素样蛋白UBQLN2通过抑制结肠癌细胞Wnt信号通路发挥抑癌作用。

Colon cancer is a malignant tumor that harms human health.In spite of significant progress in our understanding of the molecular pathogenesis,the prognosis for patients with colon cancer remains poor.Ubiquilin-2(UBQLN2)is a member of the ubiquitin family,actively implicated in the degradation of misfolded and redundant proteins through the ubiquitin-proteasome system and macroautophagy.However,the role and mechanism of UBQLN2 in colon cancer are not clear.This study was designed to explore the role of UBQLN2 in colon cancer and whether the Wnt pathway is involved.IHC and Western blotting analysis showed lower UBQLN2 expression in colon cancer tissues and cells(P<0.05),and exhibited a negative correlation of UBQLN2 expression with clinical stage and lymph node metastasis(P<0.05).CCK-8 assay and flow cytometry demonstrated that UBQLN2 expression could inhibit colon cancer cell proliferation and promote cell apoptosis(P<0.05).Western blotting analysis reveals that suppression of UBQLN2 enhances Bcl-2 expression but inhibits Bax and Wnt signaling.Taken together,these results showed that UBQLN2 inhibits proliferation and promotes apoptosis of colorectal cancer cells through suppressing the Wnt signaling pathway.