Song Xiaoyue, Li Ruhong, Liu Gang, Huang Lihua, Li Peng, Feng Wanjiang, Gao Qiujie, Xing Xiaowei
Center for Experimental Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Department of Laboratory Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Cancers (Basel). 2022 Oct 31;14(21):5368. doi: 10.3390/cancers14215368.
SUN5 was first identified as a nuclear envelope protein involved in spermatocyte division. We found that SUN5 was highly expressed in some cancers, but its function and mechanism in cancer development remain unclear. In the present study, we demonstrated that SUN5 was highly expressed in colorectal cancer (CRC) tissues and cells, as indicated by bioinformatics analysis, and SUN5 promoted cell proliferation and migration in vitro. Moreover, the overexpression of SUN5 upregulated phosphorylated ERK1/2 (pERK1/2), whereas the knockdown of SUN5 yielded the opposite results. PD0325901 decreased the level of pERK1/2 to inhibit cell proliferation and migration, which was partially reversed by SUN5 overexpression, indicating that drug resistance existed in patients with high SUN5 expression. The xenograft transplantation experiment showed that SUN5 accelerated tumor formation in vivo. Furthermore, we found that SUN5 regulated the ERK pathway via Nesprin2 mediation and promoted the nuclear translocation of pERK1/2 by interacting with Nup93. Thus, these findings indicated that highly expressed SUN5 promoted CRC proliferation and migration by regulating the ERK pathway, which may contribute to the clinical diagnosis and new treatment strategies for CRC.
SUN5最初被鉴定为一种参与精母细胞分裂的核包膜蛋白。我们发现SUN5在某些癌症中高表达，但其在癌症发展中的功能和机制仍不清楚。在本研究中，生物信息学分析表明，SUN5在结直肠癌（CRC）组织和细胞中高表达，且SUN5在体外促进细胞增殖和迁移。此外，SUN5的过表达上调了磷酸化ERK1/2（pERK1/2）的水平，而SUN5的敲低则产生相反的结果。PD0325901降低了pERK1/2的水平以抑制细胞增殖和迁移，而SUN5的过表达部分逆转了这一作用，表明SUN5高表达的患者存在耐药性。异种移植实验表明，SUN5在体内加速肿瘤形成。此外，我们发现SUN5通过Nesprin2介导调节ERK通路，并通过与Nup93相互作用促进pERK1/2的核转位。因此，这些发现表明，高表达的SUN5通过调节ERK通路促进CRC的增殖和迁移，这可能有助于CRC的临床诊断和新的治疗策略。
