Solute carrier family 34 member 2 overexpression contributes to tumor growth and poor patient survival in colorectal cancer
Solute carrier family 34 member 2 overexpression contributes to tumor growth and poor patient survival in colorectal cancer
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溶质载体家族 34 成员 2 过度表达导致结直肠癌肿瘤生长和患者生存率低
DOI：
10.1016/j.biopha.2018.01.124
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发表时间：
2018-03-01
影响因子：
7.5
通讯作者：
Wu, Zhenqian
中科院分区：
文献类型：
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作者：
Liu, Liguo;Yang, Yi;Wu, Zhenqian
溶质载体家族34成员2（SLC 34 A2）是一种众所周知的钠依赖性磷酸盐转运蛋白，最近被认为与癌症发展有关。然而，其特定的致癌作用在许多人类恶性肿瘤中仍然存在争议，目前在结直肠癌（CRC）中尚不清楚。因此，本研究首先利用Oncomine数据库确定其在癌组织中的表达，发现其在甲状腺癌、卵巢癌和肾癌中过表达，而在肺癌、乳腺癌和胰腺癌中则相反。使用qRT-PCR和蛋白质印迹，我们然后证明了其在CRC组织中的过表达，与邻近的正常组织相比（n = 20）。在一个回顾性队列中，我们纳入了190例结直肠癌患者，证明其表达与N分期显著相关。此外，SLC 34 A2高表达与较高的术后转移率相关，并且是影响患者预后的独立不利因素。在亚组分析中，SLC 34 A2的表达可以对II期和III期CRC患者的预后进行分层，但在IV期CRC中则不能。在体外细胞实验中，SLC 34 A2的敲低显著抑制HCT-116 CRC细胞的增殖和集落形成，诱导凋亡并阻滞细胞周期进程。在体内细胞试验中，SLC 34 A2的敲低显著抑制异种移植物的生长，降低Ki-67和增殖细胞核抗原（PCNA）表达，并增加凋亡率。综上所述，我们的研究表明，SLC 34 A2在CRC的发展中起着至关重要的促进作用，因此有很大的潜力进一步发展为CRC诊断和治疗的可靠生物标志物。
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.