Karyopherin alpha 2 (KPNA2) is a nuclear import factor that plays a crucial role in nucleocytoplasmic transport, as well as cell proliferation, migration, and invasion in several cancers. However, the roles of KPNA2 in breast cancer as well as the underlying molecular mechanisms have not been elucidated.

To evaluate gene expression alterations during breast carcinogenesis, KPNA2 expression was analyzed using the Gene Expression Profiling Interactive Analysis and Oncomine analyses. The correlation between methylation and expression was analyzed using the MEXPRESS tool, UALCAN cancer database, and cBioPortal browser. Then, the expression and prognostic value of KPNA2 were investigated by our own breast cancer samples using RT-PCR. KPNA2 methylation level was detected by methylation-specific PCR.

We obtained the following important results. (1) KPNA2 expression was significantly higher in breast cancer than normal samples and regulated by aberrant DNA hypomethylation of promoter region. (2) Among patients with breast cancer, those with higher KPNA2 expression had a lower survival rate. (3) The major mutation type of KPNA2 in breast cancer samples was missense mutation. (4) Homer1 was able to promote breast cancer progression may be through upregulating TPX2 expression.

Our findings suggest that aberrant DNA hypomethylation of promoter regions contributes to the aberrant expression of KPNA2 in breast cancer, which might be a potential indicator of poor prognosis.

Our findings suggest that aberrant DNA hypomethylation of promoter regions contributes to the aberrant expression of KPNA2 in breast cancer, which might be a potential indicator of poor prognosis.

Salivary adenoid cystic carcinoma (SACC), a rare cancer arising in the salivary glands, is characterized by high rates of relapse and distant metastasis. Epidermal growth factor receptor (EGFR) has been implicated in SACC carcinogenesis. However, prospective trials of EGFR-targeting therapies in SACC are limited, and the optimum regimen is unclear.

The effects of erlotinib on cell proliferation, colony formation, ALDH enzymatic activity and tumorsphere formation were investigated in SACC cells. Expression of the cancer stem cell markers Bmi-1 and Oct4 was evaluated using Western blotting.

We found that while it robustly inhibited cell growth, targeting EGFR with erlotinib enriched the ALDH

cell population and elevated the clonogenicity of SACC cells, suggesting an increase in stem cell-like potential. In addition, we found that suppression of EGFR kinase activity with erlotinib led to the activation of Notch1 signaling, leading to an increase in stem cell-like properties. Moreover, the γ-secretase inhibitor GSI treatment eliminated the erlotinib-induced increase in stem cell-like properties by decreasing Notch activity.

Our results provide an explanation for the worsened survival observed in some studies of erlotinib therapy in SACC and provide potential therapeutic strategies by combined blockade of the EGFR and Notch1 pathways.

Our results provide an explanation for the worsened survival observed in some studies of erlotinib therapy in SACC and provide potential therapeutic strategies by combined blockade of the EGFR and Notch1 pathways.

What is the optimal neoadjuvant chemotherapy (NAC) regimen for locally advanced gastric cancer (LAGC) remains debatable. The objective of this study was to compare the efficacy of docetaxel+oxaliplatin+S-1 (DOS) vs oxaliplatin+S-1 (SOX) as NAC for LAGC.

Data of 248 LAGC patients who received either DOS or SOX as NAC in our hospital between January 2010 and January 2018 were reviewed retrospectively. Propensity score matched (PSM) analysis was applied to minimize the selection bias in both groups. Prognostic factors were screened by univariate and multivariate Cox regression analyses.

Of the 248 LAGC patients included, 180 patients were subjected to the PSM analysis. Patients in DOS group showed a better tumor response to NAC, higher radical resection rate and R0 resection rate than those in SOX group. The overall survival (OS) rate in DOS group was better than that in SOX group, although the overall incidence of Grade 3/4 NAC-related toxicity in DOS group was higher, as represented by leukopenia and neutropenia. Multivariate analysis revealed that the NAC regimen, cTNM stage and the R0 resection rate were independent prognostic factors. In addition, patients with TLND less than 16 population showed a worse OS rate. Subgroup analysis indicated that patients benefited from the addition of docetaxel regardless of the clinical T stage, but those with high clinical N stages (N2-3) did not.

DOS is a safe and feasible NAC regimen for LAGC, which is worth popularizing in clinical practice.

DOS is a safe and feasible NAC regimen for LAGC, which is worth popularizing in clinical practice.

Gastric cancer (GC) is a gastrointestinal tumor. This study is aimed to explore the regulatory mechanism of long non-coding RNA BLACAT1 (BLACAT1)/microRNA-149-5p (miR-149-5p)/KIF2A cascade on GC.

The expression of BLACAT1, miR-149-5p and KIF2A in GC was detected by qRT-PCR. The proliferation, migration and invasion of GC cells in vitro were analyzed by MTT, wound-healing and transwell assay, respectively. The xenograft tumor model was constructed in nude mice to confirm the inhibition effect of BLACAT1 knockdown on GC in vivo. Then, dual-luciferase reporter assay was used to detect the interactions among BLACAT1, miR-149-5p and KIF2A. selleck compound Western blot assay was performed to determine the protein expression of KIF2A.

The expression of BLACAT1 and KIF2A was up-regulated in GC, but miR-149-5p expression was down-regulated. Silencing of BLACAT1 retarded the proliferation, migration and invasion of GC cells in vitro and the growth of tumor xenograft in vivo. Moreover, BLACAT1 acted as the molecular sponge of miR-149-5p to up-regulate KIF2A expression. At last, feedback experiments suggested that BLACAT1 accelerated the proliferation, migration and invasion of GC cells by regulating miR-149-5p/KIF2A axis.

BLACAT1 facilitated the tumorigenesis of GC through regulating miR-149-5p/KIF2A axis, which indicated BLACAT1/miR-149-5p/KIF2A cascade may be a new therapeutic target.

BLACAT1 facilitated the tumorigenesis of GC through regulating miR-149-5p/KIF2A axis, which indicated BLACAT1/miR-149-5p/KIF2A cascade may be a new therapeutic target.