Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling

Lin，Jian Jiao1; Luo，Bao Hua2; Su，Tao1; Yang，Qiong3; Zhang，Qin Fei1; Dai，Wei Yu4; Liu，Yan1; Xiang，Li1

2023

10.4251/wjgo.v15.i8.1384

World Journal of Gastrointestinal Oncology   Impact Factor & Quartile

1948-5204

BACKGROUND Altered miR-188-3p expression has been observed in various human cancers. AIM To investigate the miR-188-3p expression, its roles, and underlying molecular events in gastric cancer. METHODS 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. RESULTS 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. CONCLUSION 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.

AKT/mTOR signaling pathway Autophagy CBL expression Gastric cancer miR-188-3p Tumor cell proliferation

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English

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Guangdong Medical Research Foundation[B2019126];

WOS:001065649000006

2-s2.0-85168852133

Scopus

1.Department of Gastroenterology,The Second Affiliated Hospital of Chinese University of Hong Kong (Shenzhen Longgang District People's Hospital),Shenzhen,Guangdong Province,518172,China
2.Department of Urology,Hospital of Southern University of Science and Technology,Shenzhen,Guangdong Province,518055,China
3.Department of Gastroenterology,The Second Affiliated Hospital of the University of South China,Hengyang,Hunan Province,421001,China
4.Department of Gastroenterology,Guangdong Provincial Key Laboratory of Gastroenterology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong Province,510515,China

Lin，Jian Jiao,Luo，Bao Hua,Su，Tao,et al. Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling[J]. World Journal of Gastrointestinal Oncology,2023,15(8):1384-1399.

Lin，Jian Jiao.,Luo，Bao Hua.,Su，Tao.,Yang，Qiong.,Zhang，Qin Fei.,...&Xiang，Li.(2023).Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling.World Journal of Gastrointestinal Oncology,15(8),1384-1399.

Lin，Jian Jiao,et al."Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling".World Journal of Gastrointestinal Oncology 15.8(2023):1384-1399.