ABSTRACT
BACKGROUND: Splicing factor B subunit 4 (SF3B4) has been confirmed to participate in the progression of many cancers and is considered to be a potential target for non-small cell lung cancer (NSCLC). Thus, the role and molecular mechanism of SF3B4 in NSCLC progression deserves further study. METHODS: Quantitative real-time PCR and western blot were employed to detect the mRNA and protein levels of SF3B4, Sm-like protein 4 (LSM4) and methyltransferase-like 3 (METTL3). Cell proliferation, apoptosis, invasion, migration and stemness were tested by cell counting kit-8, colony formation, flow cytometry, transwell, wound healing, and sphere formation assays. The interaction between SF3B4 and METTL3 or LSM4 was confirmed by MeRIP, RIP and Co-IP assays. Mice xenograft models were constructed to assess the effects of METTL3 and SF3B4 on NSCLC tumorigenesis. RESULTS: SF3B4 had high expression in NSCLC tissues and was associated with the shorter overall survival of NSCLC patients. Knockdown of SF3B4 suppressed NSCLC cell proliferation, invasion, migration and stemness, while inducing apoptosis. METTL3 promoted SF3B4 mRNA stability by m6A modification, and its knockdown inhibited NSCLC cell growth, metastasis and stemness by downregulating SF3B4. SF3B4 could interact with LSM4, and sh-SF3B4-mediated the inhibition on NSCLC cell functions could be reversed by LSM4 overexpression. In addition, reduced METTL3 expression restrained NSCLC tumor growth, and this effect was reversed by SF3B4 overexpression. CONCLUSION: METTL3-stablized SF3B4 promoted NSCLC cell growth, metastasis and stemness via positively regulating LSM4.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Animals , Humans , Mice , Apoptosis , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Cell Proliferation , Lung Neoplasms/genetics , Methyltransferases/genetics , Ribonucleoproteins, Small Nuclear , RNA Splicing Factors/geneticsABSTRACT
Expression of lactate dehydrogenase (LDH) and carcinoembryonic antigen (CEA) in serum was investigated in the process of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeting for treating lung adenocarcinoma and the association between LDH, CEA and prognosis of patients was evaluated. A retrospective analysis of 89 patients with lung adenocarcinoma admitted to The First People's Hospital of Chuzhou from January 2014 to February 2015 was performed. Fifty-one patients who received resection were considered the operation group, while the other 38 patients received EGFR-TKI targeted therapy and were considered the targeted group. Electrochemiluminescence and automatic biochemical analyzer were respectively used to detect the expression of CEA and LDH in serum. The therapeutic effective rates and the expression levels of LDH and CEA of the patients were compared. The patients in the targeted group were divided into LDH high-expression group, LDH low-expression group, CEA high-expression group and CEA low-expression group according to the median of the expression levels of LDH and CEA. The therapeutic effective rate in LDH high-expression group (65.00%) was significantly lower than that in LDH low-expression group (100.00%) (P=0.004). The therapeutic effective rate in CEA high-expression group (64.71%) was significantly lower than that in CEA low-expression group (95.24%) (P=0.016). The 3-year overall mortality rate in LDH high-expression group (47.37%) was significantly higher than that in LDH low-expression group (11.11%) (P=0.034). The 3-year overall mortality rate in CEA high-expression group (56.25%) was significantly higher than that in CEA low-expression group (4.76%) (P=0.020). The levels of CEA and LDH in serum were abnormally expressed in the process of the treatment of lung adenocarcinoma targeted by EGFR-TKI, which had great significance for monitoring the efficacy and prognosis of the treatment of lung adenocarcinoma targeted by EGFR-TKI.
