Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy. However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients. Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation. Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome. This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
Human non-small cell lung carcinoma (NSCLC) is one of the most common cancer worldwide. In previous studies, lovastatin, acting as an inhibitor of 3-hydroxy-3-methylglutaryl Co A (HMG-CoA) reductase, exhibited significant antitumor activity during tumorigenesis. However, whether or not this effect is mediated through changes in minichromosome maintenance (MCM) 2 expression remains unclear. The present study investigated whether lovastatin inhibits proliferation due to MCM2 in NSCLCs. We first assessed the effects of lovastatin on cell anti-proliferation, cell cycle progression and apoptosis in NSCLC cells. We found, by quantitative RT-PCR and western blot analysis, that lovastatin treatment markedly and consistently inhibited the expression of MCM2. Then, to further explore the anticancer mechanism of lovastatin involving MCM2, we silenced MCM2 by siRNA in two cell lines (A549 and GLC-82). Silencing of MCM2 triggered G1/S arrest. Following further examination of cell cycle-related factors, MCM2 knockdown inhibited protein retinoblastoma (Rb), cyclin D1 and CDK4 expression, but increased p21 and p53 expression, suggesting that siMCM2 indeed triggered cell cycle arrest. In addition, siMCM2 induced apoptosis. Finally, lovastatin treatment increased p-JNK, which is involved in the downregulation of MCM2. In conclusion, our data suggest that MCM2 may be a novel therapeutic target of lovastatin treatment in NSCLCs.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that, when dysregulated, are involved in the initiation and progression of various cancers, including lung cancer, in humans. In the current study, qRT-PCR was performed to measure miR-211 expression in human non-small cell lung cancer (NSCLC) cell lines and tissues. Cell proliferation, cell cycle, colony formation, and invasion were performed to detect the functional role of miR-211 in human NSCLC cell line. We used luciferase reporter assay to find the potential target of miR-211. We found that miR-211 expression was upregulated in human non-small cell lung cancer (NSCLC) cell lines and tissues. The overexpression of miR-211 enhanced NSCLC cell proliferation, colony formation, and invasion. SRC kinase signaling inhibitor 1 (SRCIN1) was identified as a direct target of miR-211. SRCIN1 silencing promoted cell proliferation, and SRCIN1 expression was downregulated in human NSCLC cell lines. Thus, miR-211 may function as an oncogenic miRNA in NSCLC, partly by regulating SRCIN1, and the modulation of miR-211 expression represents a potential strategy for the treatment of NSCLC patients.
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