MiR-137 mediated high expression of TIGD1 promotes migration, invasion, and suppresses apoptosis of lung adenocarcinoma

Objectives

Tigger transposable element-derived 1 (TIGD1) expression and its underlying functions and regulatory mechanisms in lung adenocarcinoma (LUAD) remain unknown. Therefore, we intended to explore the expression, potential functions, and regulatory mechanisms of TIGD1 in LUAD.

Materials and methods

TIGD1 expression in LUAD tissues was determined by immunohistochemistry analysis of a tissue microarray. Functional experiments were conducted to determine how TIGD1 affects LUAD tumorigenesis and metastasis. The molecular mechanisms by which TIGD1 induces LUAD progression were determined.

Results

TIGD1 was upregulated in LUAD tissues and was related to lymph node metastases. TIGD1 knockdown suppressed LUAD cell proliferation, migration, and invasion, while promoted cell apoptosis. Furthermore, decreased metastatic nodules were observed in the TIGD1 knockdown mouse metastasis model. Moreover, microarray analysis was performed to determine the potential downstream genes of TIGD1 in LUAD. Hallmark pathway analysis revealed that the downstream genes of TIGD1 were involved in epithelial-mesenchymal transition (EMT). Western blotting confirmed that vimentin and TWIST was downregulated in TIGD1 knockdown cells, while E-cadherin was upregulated. Ingenuity pathway and hallmark pathway analyses revealed that TIGD1 regulated the interleukin-6 signaling pathway and related gene members. Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay indicated that downregulation of TIGD1 decreased interleukin-6 and CXCL1 expression. TIGD1 expression was negatively correlated with immune infiltration in LUAD. The upstream microRNA of TIGD1 was predicted, and subsequent luciferase reporter gene experiments confirmed the interactions between miR-137 and TIGD1. The expression of miR-137 was significantly downregulated in LUAD tissues and miR-137 suppressed the proliferation, migration, and invasion of LUAD cells, partially through negatively regulating the expression of TIGD1.

Conclusion

Our findings suggest that TIGD1, which was regulated by miR-137, contributed to LUAD progression by promoting cell proliferation, migration, invasion, and EMT and suppressing cell apoptosis.