Investigating the anti-cancer potential of sulfatase 1 and its underlying mechanism in non-small cell lung cancer.

Abstract

Objective: Patients with non-small cell lung cancer (NSCLC) have poor prognoses. Sulfatase 1 (SULF1) is an extracellular neutral sulfatase and is involved in multiple physiological processes. Hence, this study investigated the function and possible mechanisms of SULF1 in NSCLC.

Material and methods: Difference in SULF1 expression level between tumors and normal lung tissues was analyzed through bioinformatics and clinical sampling, and the effects of SULF1 expression on prognosis were investigated through Kaplan-Meier analysis. SULF1 level in NSCLC cells was modulated through small interfering ribonucleic acid interference. NSC228155, which is an epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway agonist, was for handling NSCLC cells. SULF1 expression level was tested through quantitative reverse transcriptase real-time polymerase chain reaction. Cell proliferation, migration, and invasion were evaluated with cell counting kit-8, 5-ethynyl-2-deoxyuridine, and transwell assays, and the levels of epithelial-to-mesenchymal transition (EMT)- and EGFR/MAPK pathway-related proteins were detected through Western blot.

Results: Bioinformatics and clinical samples showed that NSCLC tumor tissues had elevated SULF1 expression levels relative to those of normal tissues (P < 0.05). Patients with NSCLC and high SULF1 expression levels experienced poorer prognosis than those of low SULF1 expression levels (P < 0.05). SULF1 knockdown repressed the malignant biological behavior, including proliferation, migration, and invasion, of the NSCLC cells (P < 0.05). Mechanistically, SULF1 knockdown augmented E-cadherin level and abated N-cadherin and vimentin protein levels (P < 0.05). These results confirmed that EMT was inhibited. In addition, the knockdown of SULF1 reduced the phosphorylation of EGFR, extracellular signal-regulated kinase, p38 MAPK and c-Jun N-terminal kinase, and NSC228155 partially reversed these changes, which were affected by SULF1 knockdown. Meanwhile, NSC228155 partially reversed the inhibition of EMT, migration, and invasion affected by SULF1 knockdown.

Conclusion: SULF1 knockdown inhibits the proliferation, migration, invasion, and EMT of NSCLC cells by inactivating EGFR/MAPK pathway.