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PHLPP2 通过竞争内源性 RNA 网络调控在结肠癌发病机制中的作用。

PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer.

机构信息

Department of Laboratory Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China.

Department of General Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China.

出版信息

Aging (Albany NY). 2020 Jul 7;12(13):12812-12840. doi: 10.18632/aging.103246.

DOI:10.18632/aging.103246
PMID:32633726
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7377866/
Abstract

Recently, homologous pleckstrin-homology (PH)-domain leucine-rich-repeat protein phosphatases (PHLPP2) has been reported as a tumor suppressor in colon cancer. This study aimed to unravel the possible involvement of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) regulating PHLPP2 in colon cancer. Expressions of candidate lncRNAs and miRNAs were verified by the RT-qPCR and Western blot analyses in colon cancer. The roles of candidate genes in colon cancer were investigated in HT-29 cells and in mouse tumor xenograft model . PHLPP2, a target of miR-141 and miR-424, was downregulated in colon cancer. PHLPP2 upregulation and miR-141 and miR-424 downregulation suppressed the colon cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition, and promote cell apoptosis, which also resulted in suppression of tumor metastasis and formation. Furthermore, LINC00402, LINC00461, and SFTA1P were identified as the targets of miR-141 and miR-424 and acted as competitive endogenous RNAs (ceRNAs) of PHLPP2. The upregulation of LINC00402, LINC00461, and SFTA1P was verified to enhance the suppressive effects of PHLPP2 in the pathogenesis of colon cancer. Conjointly, our results demonstrated the suppressive effects of PHLPP2 in colon cancer and proved that LINC00402, LINC00461, and SFTA1P acted as ceRNAs of PHLPP2 by competitive binding to miR-141 and miR-424.

摘要

最近，同源pleckstrin-homology (PH)-结构域富含亮氨酸重复蛋白磷酸酶（PHLPP2）被报道为结肠癌的肿瘤抑制因子。本研究旨在揭示调节结肠癌中 PHLPP2 的长链非编码 RNA（lncRNA）和 microRNA（miRNA）的可能参与。通过 RT-qPCR 和 Western blot 分析在结肠癌中验证候选 lncRNA 和 miRNA 的表达。在 HT-29 细胞和小鼠肿瘤异种移植模型中研究候选基因在结肠癌中的作用。miR-141 和 miR-424 的靶标 PHLPP2 在结肠癌中下调。PHLPP2 的上调和 miR-141 和 miR-424 的下调抑制了结肠癌细胞的增殖、迁移、侵袭和上皮-间充质转化，并促进细胞凋亡，这也导致肿瘤转移和形成的抑制。此外，LINC00402、LINC00461 和 SFTA1P 被鉴定为 miR-141 和 miR-424 的靶标，并作为 PHLPP2 的竞争性内源 RNA（ceRNA）。上调 LINC00402、LINC00461 和 SFTA1P 被证实可增强 PHLPP2 在结肠癌发病机制中的抑制作用。总之，我们的研究结果表明 PHLPP2 在结肠癌中具有抑制作用，并证明 LINC00402、LINC00461 和 SFTA1P 通过竞争性结合 miR-141 和 miR-424 作为 PHLPP2 的 ceRNA。

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