Downregulation of miR-139 in lung cancer promotes metastasis via ERBB2/Rac1/NF-κB signaling axis.

BACKGROUND

Tumor metastasis is a key factor in cancer progression, yet its molecular mechanisms are not fully understood. ERBB2-positive lung cancer exhibits aggressive behavior, and the role of miR-139 in its metastasis requires investigation.

OBJECTIVES

This study aimed to explore the function of miR-139 in ERBB2-positive lung cancer and its underlying molecular mechanism involving the ERBB2/Rac1/NF-κB signaling axis.

METHODS

The study utilized A549 lung cancer cells and tissue samples from 106 lung cancer patients. Methods included RT-PCR, bioinformatics analysis, dual-luciferase reporter assay, Western blot, cell migration/invasion assays, wound healing tests, Rac1 activity assays, and rescue experiments using Rac1-Q61L.

RESULTS

MiR-139 expression was significantly downregulated in lung cancer tissues, especially in lymph node metastases (P<0.01). MiR-139 directly targeted the 3'UTR of ERBB2 and inhibited its expression (P<0.01). Overexpression of miR-139 reduced Rac1 activity (P<0.01) without affecting RhoA or Cdc42, and decreased NF-κB signaling activity in ERBB2-positive tissues. MiR-139 overexpression significantly suppressed cell migration and invasion (P<0.01), an effect partially reversed by Rac1-Q61L.

CONCLUSION

MiR-139 inhibits lung cancer cell migration and invasion by targeting ERBB2, suppressing Rac1 activity, and downregulating NF-κB signaling. Its downregulation promotes metastasis through the ERBB2/Rac1/NF-κB axis.