Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.
Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8664-8674. doi: 10.26355/eurrev_201812_16631.
Emerging evidence has shown that Podocalyxin-like (PODXL) plays an important role in the development and progression of several tumors, including colorectal cancer (CRC). However, its potential role in CRC is still not documented. The present study aimed to explore biological functions and molecular mechanisms in CRC development.
Microarray data were downloaded from TCGA datasets and statistically analyzed. RT-PCR was performed to detect the expression of PODXL and miR-138. Lost-function assay was used to explore the roles of PODXL on CRC behavior. Bioinformatics tools were used to identify the upstream miRNAs and the relationship between PODXL and miR-138 was detected via Dual-Luciferase assay, Western blot and rescue experiments.
PODXL expression was significantly up-regulated in both CRC tissues and cell lines. In vitro experiments showed the knockdown of PODXL suppressed reduces CRC tumor growth, metastasis and EMT, and promoted apoptosis. Moreover, PODXL was predicted and confirmed to be a target of miR-138. In addition, ectopic expression of PODXL significantly reversed the suppression of cell proliferation and metastasis caused by the miR-138 over-expression.
We provided important evidence that PODXL, targeted by miR-138, acted as a tumor promoter in CRC by suppressing CRC cells proliferation and metastasis, which may provide a novel potential target for diagnostic and therapeutic applications in CRC.
有研究表明 Podocalyxin-like (PODXL) 在多种肿瘤的发生和发展中发挥着重要作用，包括结直肠癌（CRC）。然而，其在 CRC 中的潜在作用尚未得到证实。本研究旨在探讨 PODXL 在 CRC 发展中的生物学功能和分子机制。
从 TCGA 数据库中下载微阵列数据并进行统计学分析。采用 RT-PCR 检测 PODXL 和 miR-138 的表达。通过失活功能实验来探索 PODXL 对 CRC 行为的作用。利用生物信息学工具来识别上游 miRNA，并通过双荧光素酶报告基因实验、Western blot 和挽救实验来检测 PODXL 和 miR-138 之间的关系。
PODXL 在 CRC 组织和细胞系中均呈显著高表达。体外实验表明，PODXL 的敲低可抑制 CRC 肿瘤生长、转移和 EMT，并促进细胞凋亡。此外，PODXL 被预测并确认为 miR-138 的靶基因。此外，外源性表达 PODXL 可显著逆转 miR-138 过表达引起的细胞增殖和转移抑制作用。
我们提供了重要证据，表明 miR-138 靶向的 PODXL 通过抑制 CRC 细胞的增殖和转移，在 CRC 中发挥促肿瘤作用，这可能为 CRC 的诊断和治疗应用提供新的潜在靶点。
