TMEM33, an oncogene regulated by miR-214-3p, promotes the progression of lung adenocarcinoma through the Wnt/β-catenin signaling pathway

Lung cancer remains a major factor causing cancer-associated mortality globally. While there have been advancements in treatment options, advanced lung cancer patients still have poor outcomes. This study aims to investigate the potential role of Transmembrane protein 33 (TMEM33) in the development of lung adenocarcinoma.

We leveraged The Cancer Genome Atlas (TCGA) database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma (LUAD). Cell proliferation, invasiveness, and sphere formation were analyzed by various experiments. The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay, immunoblotting, and real-time quantitative PCR (RT-qPCR). Additionally, TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.

TMEM33 showed high expression within both LUAD tissues and cells, with its expression correlating with poor patient survival outcomes. Silencing TMEM33 resulted in significant reductions in cell proliferation, invasiveness, and stem-like properties. Further investigation suggested that miR-214-3p negatively regulated TMEM33. In both cellular and animal models, we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells, impeding tumor growth and inhibiting metastasis in the mouse model. Moreover, reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway, providing insights into TMEM33’s mechanistic role in LUAD.

TMEM33 functions as an oncogene, which is under the negative regulation of miR-214-3p, to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.