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miR-124 通过靶向 PRRX1 增敏人结直肠癌细胞。

MiR-124 Radiosensitizes human colorectal cancer cells by targeting PRRX1.

机构信息

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.

出版信息

PLoS One. 2014 Apr 4;9(4):e93917. doi: 10.1371/journal.pone.0093917. eCollection 2014.

Abstract

One of the challenges in the treatment of colorectal cancer patients is that these tumors show resistance to radiation. MicroRNAs (miRNAs) are involved in essential biological activities, including chemoresistance and radioresistance. Several research studies have indicated that miRNA played an important role in sensitizing cellular response to ionizing radiation (IR). In this study, we found that miR-124 was significantly down-regulated both in CRC-derived cell lines and clinical CRC samples compared with adjacent non-tumor colorectal tissues, MiR-124 could sensitize human colorectal cancer cells to IR in vitro and in vivo. We identified PRRX1, a new EMT inducer and stemness regulator as a novel direct target of miR-124 by using target prediction algorithms and luciferase assay. PRRX1 knockdown could sensitize CRC cells to IR similar to the effects caused by miR-124. Overexpression of PRRX1 in stably overexpressed-miR-124 cell lines could rescue the effects of radiosensitivity enhancement brought by miR-124. Taking these observations into consideration, we illustrated that miR-124 could increase the radiosensitivity of CRC cells by blocking the expression of PRRX1, which indicated miR-124 could act as a great therapeutic target for CRC patients.

摘要

结直肠癌患者治疗面临的挑战之一是这些肿瘤对辐射有抵抗力。microRNAs(miRNAs)参与了包括化疗耐药性和放射耐药性在内的重要生物学活动。一些研究表明,miRNA 在使细胞对电离辐射(IR)的反应敏感方面发挥了重要作用。在这项研究中,我们发现与相邻非肿瘤结直肠组织相比,CRC 衍生细胞系和临床 CRC 样本中的 miR-124 均明显下调。miR-124 可在体外和体内使人类结直肠癌细胞对 IR 敏感。我们通过靶标预测算法和荧光素酶测定鉴定了 PRRX1,一种新的 EMT 诱导因子和干性调节剂,是 miR-124 的新型直接靶标。PRRX1 敲低可使 CRC 细胞对 IR 敏感,类似于 miR-124 引起的作用。在稳定过表达 miR-124 的细胞系中过表达 PRRX1 可挽救 miR-124 增强放射敏感性的作用。考虑到这些观察结果,我们说明 miR-124 可通过阻断 PRRX1 的表达来增加 CRC 细胞的放射敏感性,这表明 miR-124 可作为 CRC 患者的重要治疗靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/595a/3976353/213d2fb18d82/pone.0093917.g001.jpg

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