Cancer Biomark. 2019;26(1):1-9. doi: 10.3233/CBM-182279.
Gastric cancer (GC) is one of the leading causes of cancer-related death in East Asia and some South American countries, but its mechanism has not been clarified clearly. Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1), a co-regulatory molecule of estrogen receptor α (ER α), is up-regulated in series of cancers such as endometrial carcinoma, ovarian cancer, colorectal cancer, breast cancer, and non-small cell lung cancer. However, PELP1's role in GC is still obscure, and its aberrant expression in cancers also remains to be explained.
Immunohistochemical staining and Real-time PCR were used to compare the expression level of PELP1 in GC tissues and adjacent tissues. Western blot was used to detect the expression of PELP1 in cell lines. Kaplan-meier analysis and chi-square test were applied to evaluate the potential of PELP1 to function as a cancer biomarker. RNA interference was used to inhibit PELP1 expression in GC cells, followed by detecting cell proliferation, apoptosis, migration and invasion. Luciferase assay was conducted to validate whether miR-15 family members can directly target PELP1.
In this study, we validated that PELP1 was significantly up-regulated in GC samples and cell lines. It was also demonstrated that the up-regulation of PELP1 was associated with several clinicopathologic features such as tumor diameter (P< 0.001), serum CEA level (P= 0.034), and lymphatic metastasis (P= 0.0009) of GC patients, and its high expression was correlated with shorter disease-free survival and overall survival of the patients. Knockdown of PELP1 remarkably arrested the proliferationï¼ migration and invasion, while promoted apoptosis. We also confirmed that miR-15 family microRNAs, most of which were down-regulated and tumor suppressor in cancers, were posttranscriptional regulators of PELP1.
In conclusion, we demonstrated that PELP1 was an oncogene of GC associated with patients' prognosis and miR-15 family members contributed to its aberrant expression in cancers.
胃癌（GC）是东亚和一些南美国家癌症相关死亡的主要原因之一，但其发病机制尚不清楚。脯氨酸、谷氨酸和亮氨酸丰富蛋白 1（PELP1）是雌激素受体α（ERα）的共调节分子，在子宫内膜癌、卵巢癌、结直肠癌、乳腺癌和非小细胞肺癌等一系列癌症中上调。然而，PELP1 在 GC 中的作用仍然不清楚，其在癌症中的异常表达也有待解释。
采用免疫组织化学染色和实时 PCR 比较 GC 组织和相邻组织中 PELP1 的表达水平。Western blot 检测细胞系中 PELP1 的表达。Kaplan-meier 分析和卡方检验评估 PELP1 作为癌症生物标志物的潜力。用 RNA 干扰抑制 GC 细胞中 PELP1 的表达，然后检测细胞增殖、凋亡、迁移和侵袭。荧光素酶测定验证 miR-15 家族成员是否能直接靶向 PELP1。
本研究验证了 PELP1 在 GC 样本和细胞系中显著上调。还表明 PELP1 的上调与 GC 患者的几个临床病理特征有关，如肿瘤直径（P<0.001）、血清 CEA 水平（P=0.034）和淋巴转移（P=0.0009），其高表达与患者无病生存率和总生存率较短有关。PELP1 的敲低显著抑制了增殖、迁移和侵袭，同时促进了凋亡。我们还证实，miR-15 家族 microRNAs 大多数在癌症中下调且作为肿瘤抑制因子，是 PELP1 的转录后调节因子。
总之，我们证明 PELP1 是与患者预后相关的 GC 致癌基因，miR-15 家族成员导致其在癌症中异常表达。
