Abstract: Background and purpose: Transforming growth factor β regulator 4 (TBRG4) is a regulator of transforming growth factor β. In recent years, studies have found that TBRG4 expression is closely related to tumors, but there are few studies on the relationship between TBRG4 and lung adenocarcinoma. Therefore, this paper aimed to study the role of TBRG4 in lung adenocarcinoma and related mechanism. Methods: Clinical samples of patients with non-small cell lung cancer (NSCLC), including tumors and adjacent tissues, were collected. Immunohistochemistry was used to detect the expression of TBRG4. The TBRG4 genespecific interference vector was constructed with lentivirus as vector, and the specific interference vector and empty vector were transfected into NCI-H1299 cells. Cell counting kit-8 (CCK-8) was used to detect the cell growth in each group. The cell clone formation experiment was used to compare the cell clone formation ability in each group. Apoptosis was detected by Annexin Ⅴ-FITC/PI double staining combined with flow cytometry. PI/RNase single staining was used to detect cell cycle. Western blot was used to detect phosphatase and tensin homolog deleted on chromosome ten (PTEN) signaling pathway-related protein expression. Results: TBRG4 protein was up-regulated in NSCLC patients' cancer tissues. Downregulation of TBRG4 inhibited H1299 cell proliferation and cell clonality, promoted apoptosis, and caused H1299 cell cycle arrest in G₀/G₁ phase. The protein expression levels of PTEN, RAP1A and IGF2 were up-regulated (P<0.05). Conclusion: TBRG4 may be involved in the development of lung cancer, and its expression in lung cancer tissues of patients with NSCLC is significantly higher than that in adjacent tissues. TBRG4 plays an important role in the biological behavior, such as proliferation and apoptosis of lung cancer cells. TBRG4 may be a  potential target for the treatment of lung cancer.

Key words: TBRG4, Non-small cell lung cancer, RNA interference, Cell proliferation, Cell apoptosis