PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer
PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer
复制标题
PHLPP2在结肠癌的发病机制中受到竞争性内源RNA网络的调节
DOI：
10.18632/aging.103246
复制
发表时间：
2020-07
期刊：
影响因子：
5.2
通讯作者：
Zhou Lin
中科院分区：
文献类型：
--
作者：
Wu Hong-Kun;Liu Chang;Li Xin-Xing;Ji Wei;Xin Chen-De;Hu Zhi-Qian;Zhou Lin
最近，同源pleckstrin-homology（PH）-domain leucine-rich-repeat protein phosphatases（PHLPP 2）被报道为结肠癌的肿瘤抑制因子。本研究旨在阐明长链非编码RNA（lncRNA）和microRNA（miRNAs）调控PHLPP 2在结肠癌中的可能参与。通过RT-qPCR和Western blot分析验证候选lncRNA和miRNAs在结肠癌中的表达。在体外HT-29细胞和体内小鼠肿瘤移植模型中研究候选基因在结肠癌中的作用。PHLPP 2是miR-141和miR-424的靶点，在结肠癌中下调。PHLPP 2的上调和miR-141、miR-424的下调抑制了结肠癌细胞的增殖、迁移、侵袭和上皮间质转化，促进细胞凋亡，从而抑制了肿瘤的转移和形成。此外，LINC 00402、LINC 00461和SFTA 1 P被鉴定为miR-141和miR-424的靶点，并充当PHLPP 2的竞争性内源RNA（ceRNA）。证实LINC 00402、LINC 00461和SFTA 1 P的上调增强了PHLPP 2在结肠癌发病机制中的抑制作用。同时，我们的结果证明了PHLPP 2在结肠癌中的抑制作用，并证明LINC 00402、LINC 00461和SFTA 1 P通过与miR-141和miR-424竞争性结合而充当PHLPP 2的ceRNA。
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 in vitro and in mouse tumor xenograft model in vivo. 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.
登录
查看更多内容
人类癌症中竞争性内源性 RNA 网络：假设、验证和观点。
影响因子：
--
作者：
Yang C;Wu D;Gao L;Liu X;Jin Y;Wang D;Wang T;Li X
通讯作者：
Li X
影响因子：
3.7
作者：
Oneyama C;Kito Y;Asai R;Ikeda J;Yoshida T;Okuzaki D;Kokuda R;Kakumoto K;Takayama K;Inoue S;Morii E;Okada M
通讯作者：
Okada M
影响因子：
3.1
作者：
Wang, Li-Xin;Wan, Chuan;Li, Yang
通讯作者：
Li, Yang
影响因子：
3
作者：
Wu Pp;Zhu Hy;Sun Xf;Chen Lx;Q. Zhou;Jie Chen
通讯作者：
Wu Pp;Zhu Hy;Sun Xf;Chen Lx;Q. Zhou;Jie Chen
影响因子：
7
作者：
Wiseman, Martin
通讯作者：
Wiseman, Martin