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

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 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 ( 0.001), tumor differentiation ( 0.001), lymph node metastasis ( = 0.033), tumor node metastasis stage (I/II III/IV, = 0.024), and American Joint Committee on Cancer stage (I/II III/IV, = 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 data confirmed antitumor activity CBL downregulation in gastric cancer.

CONCLUSION

The current data provides , , and evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.