Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling.
Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling.
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DOI：
10.4251/wjgo.v15.i8.1384
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发表时间：
2023-08-15
影响因子：
3
通讯作者：
Xiang L
中科院分区：
文献类型：
--
作者：
Lin JJ;Luo BH;Su T;Yang Q;Zhang QF;Dai WY;Liu Y;Xiang L
在多种人类癌症中观察到 miR-188-3p 表达发生改变。研究胃癌中 miR-188-3p 的表达、其作用和潜在分子事件。收集 50 个胃癌组织和配对的正常组织来分析 miR-188-3p 和 CBL 的表达。使用正常细胞和胃癌细胞通过不同的测定来操纵 miR-188-3p 和 CBL 表达。通过生物信息学方法预测 miR-188-3p 和 CBL 之间的关系，并使用荧光素酶基因报告测定法进行证实。 Kaplan-Meier 分析用于将 miR-188-3p 或 CBL 表达与患者生存相关联。使用裸鼠肿瘤细胞异种移植测定来证实体外数据。研究发现，与健康人相比，胃癌患者、组织和细胞系中的 MiR-188-3p 含量较低。它与胃癌患者的总生存期（P < 0.001）、肿瘤分化程度（P < 0.001）、淋巴结转移（P = 0.033）、肿瘤淋巴结转移分期（I/II vs III/IV，P = 0.024）和美国癌症联合委员会分期（I/II vs III/IV，P = 0.03）相关。转染 miR-188-3p 模拟物可减少肿瘤细胞的生长和侵袭，同时诱导细胞凋亡和自噬。 CBL 被确定为 miR-188-3p 的直接靶标，其表达通过 Akt/mTOR 信号通路失活诱导肿瘤细胞凋亡和自噬，从而拮抗 miR-188-3p 对胃癌 (GC) 细胞增殖的影响。体内数据证实了通过下调 CBL 在胃癌中的抗肿瘤活性。目前的数据提供了 miR-188-3p 作为肿瘤抑制基因或在 GC 中具有抗肿瘤活性的离体、体外和体内证据。
Altered miR-188-3p expression has been observed in various human cancers. To investigate the miR-188-3p expression, its roles, and underlying molecular events in gastric cancer. Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression. Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays. The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay. A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival. A nude mouse tumor cell xenograft assay was used to confirm the in vitro data. MiR-188-3p was found to be lower in the plasma of gastric cancer patients, tissues, and cell lines compared to their healthy counterparts. It was associated with overall survival of gastric cancer patients (P < 0.001), tumor differentiation (P < 0.001), lymph node metastasis (P = 0.033), tumor node metastasis stage (I/II vs III/IV, P = 0.024), and American Joint Committee on Cancer stage (I/II vs III/IV, P = 0.03). Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy. CBL was identified as a direct target of miR-188-3p, with its expression antagonizing the effects of miR-188-3p on gastric cancer (GC) cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway. The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer. The current data provides ex vivo, in vitro, and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.
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DOI：
10.18632/aging.202426
发表时间：
2021-02-01
期刊：
Aging
影响因子：
--
作者：
Lin J;Zhu H;Hong L;Tang W;Wang J;Hu H;Wu X;Chen Y;Liu G;Yang Q;Li J;Wang Y;Lin Z;Xiao Y;Dai W;Huang M;Li G;Li A;Wang J;Xiang L;Liu S
通讯作者：
Liu S
STAT3诱导的lncRNA HAGLROS过表达通过mTOR信号介导的自噬抑制促进胃癌细胞的恶性进展
影响因子：
37.3
作者：
Chen JF;Wu P;Xia R;Yang J;Huo XY;Gu DY;Tang CJ;De W;Yang F
通讯作者：
Yang F
影响因子：
78.5
作者：
Mathew, Robin;Karantza-Wadsworth, Vassiliki;White, Eileen
通讯作者：
White, Eileen
影响因子：
3.5
作者：
Ito, R;Nakayama, H;Yasui, W
通讯作者：
Yasui, W
影响因子：
13.3
作者：
Ahumada-Castro, Ulises;Silva-Pavez, Eduardo;Cardenas, Cesar
通讯作者：
Cardenas, Cesar