MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Non-small-cell lung cancer (NSCLC) presents a significant mortality challenge, with drug resistance being a primary treatment obstacle.
• High mobility group box-1 (HMGB1) protein contributes to NSCLC drug resistance by promoting autophagy.
• Understanding the regulatory mechanisms of autophagy in NSCLC is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the role of microRNA-142-3p (miR-142-3p) in regulating HMGB1-mediated autophagy in NSCLC cells.
• To assess the impact of miR-142-3p on drug resistance in NSCLC, both in vitro and in vivo.
• To elucidate the molecular pathway through which miR-142-3p influences autophagy and chemo-sensitivity.

Main Methods:

• In silico analysis identified HMGB1 as a potential target of miR-142-3p.
• Luciferase reporter assays confirmed direct targeting of HMGB1 by miR-142-3p in NSCLC cells.
• Experiments involved miR-142-3p overexpression/knockdown, HMGB1 manipulation, autophagy assessment, and analysis of the PI3K/Akt/mTOR pathway.

Main Results:

• miR-142-3p directly downregulates HMGB1 expression, suppressing starvation-induced autophagy in NSCLC cells.
• Overexpression of miR-142-3p or knockdown of HMGB1 activates the PI3K/Akt/mTOR pathway.
• miR-142-3p overexpression enhanced chemo-sensitivity and inhibited drug-induced autophagy in NSCLC models.

Conclusions:

• miR-142-3p acts as a negative regulator of autophagy in NSCLC by targeting HMGB1 and modulating the PI3K/Akt/mTOR pathway.
• Overexpression of miR-142-3p demonstrates therapeutic potential by increasing chemo-sensitivity and overcoming drug resistance in NSCLC.
• Targeting miR-142-3p offers a promising strategy for combating acquired chemo-resistance in non-small-cell lung cancer.