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溶质载体家族 34 成员 2 过表达促进结直肠癌肿瘤生长和患者生存不良。

Solute carrier family 34 member 2 overexpression contributes to tumor growth and poor patient survival in colorectal cancer.

机构信息

Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Department of Oncological Surgery, Kunshan Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Kunshan, Jiangsu, China.

出版信息

Biomed Pharmacother. 2018 Mar;99:645-654. doi: 10.1016/j.biopha.2018.01.124. Epub 2018 Feb 20.

Abstract

Solute carrier family 34 member 2 (SLC34A2) is a well-known sodium-dependent phosphate transporter that has recently been linked to cancer development. However, its specific oncogenic role remains controversial in numerous human malignancies, and is currently unknown in colorectal cancer (CRC). Therefore, in this study we firstly used Oncomine database to determine its expression in cancer tissues and found it is overexpressed in thyroid, ovarian and renal cancer, while it is opposite in lung, breast and pancreas cancer. Using qRT-PCR and western blot, we then demonstrated its overexpression in CRC tissues as compared with adjacent normal tissues (n = 20). In a retrospective cohort enrolling 190 CRC patients, we proved its expression was significantly correlated with N stage. Furthermore, high SLC34A2 expression is associated with higher postoperative metastasis rate and serves as an independent adverse factor affecting patient prognosis. In subgroup analysis, SLC34A2 expression could stratify the patient prognosis in stage II and III CRC, but failed in stage IV CRC. In cellular assays in vitro, knockdown of SLC34A2 dramatically inhibited the proliferation and colony formation, induced the apoptosis and arrests the cell cycle progression of HCT-116 CRC cells. In cellular assays in vivo, knockdown of SLC34A2 significantly inhibited the growth of xenografts, decreasing Ki-67 and proliferating cell nuclear antigen (PCNA) expression and increasing apoptosis rate. Taken together, our study indicates SLC34A2 plays a crucial promoting role in CRC development and therefore has great potential to be further developed as a reliable biomarker for CRC diagnosis and treatment.

摘要

溶质载体家族 34 成员 2(SLC34A2)是一种众所周知的钠依赖性磷酸盐转运蛋白,最近与癌症的发展有关。然而,其在许多人类恶性肿瘤中的具体致癌作用仍存在争议,在结直肠癌(CRC)中目前尚不清楚。因此,在这项研究中,我们首先使用 Oncomine 数据库来确定其在癌症组织中的表达,发现它在甲状腺癌、卵巢癌和肾癌中过度表达,而在肺癌、乳腺癌和胰腺癌中则相反。使用 qRT-PCR 和 Western blot,我们随后证明其在 CRC 组织中的表达高于相邻正常组织(n=20)。在一项纳入 190 例 CRC 患者的回顾性队列研究中,我们证明其表达与 N 分期显著相关。此外,SLC34A2 表达高与术后转移率较高有关,是影响患者预后的独立不良因素。在亚组分析中,SLC34A2 表达可分层 II 期和 III 期 CRC 患者的预后,但在 IV 期 CRC 中无效。在体外细胞实验中,SLC34A2 的敲低显著抑制 HCT-116 CRC 细胞的增殖和集落形成,诱导细胞凋亡并阻滞细胞周期进程。在体内细胞实验中,SLC34A2 的敲低显著抑制异种移植的生长,降低 Ki-67 和增殖细胞核抗原(PCNA)的表达,增加细胞凋亡率。总之,我们的研究表明 SLC34A2 在 CRC 发展中发挥关键促进作用,因此具有作为 CRC 诊断和治疗可靠生物标志物进一步开发的巨大潜力。

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