Transcription factor HOXC10 activates the expression of MTFR2 to regulate the proliferation, invasion and migration of colorectal cancer cells.

HOXC10 and mitochondrial fission regulator 2 (MTFR2) have been reported to be abnormally expressed in multiple types of cancer tissues. However, the effects of HOXC10 and MTFR2 on colorectal cancer (CRC) remain poorly understood. Therefore, the present study aimed to investigate the expression of HOXC10 and MTFR2 in CRC tissues and cells, and analyze their effects on CRC cell proliferation, invasion and migration. Reverse transcription­quantitative PCR and western blotting were used to detect the expression levels of MTFR2 and HOXC10 in tissues and cells. To investigate the association between MTFR2 and HOXC10, short hairpin RNA­MTFR2 and overexpression vector­HOXC10 were transfected into the cells, respectively. Furthermore, western blotting was performed to detect the expression levels of invasion­associated proteins. The proliferation, clone formation, invasion and migration of colorectal cancer cells were in turn analyzed by the Cell Counting Kit­8, clone formation, wound healing and Transwell assays. Japan Automotive Software Platform and Architecture software predicted the binding sites between HOXC10 and MTFR2, which was confirmed by the dual­luciferase reporter assay and chromatin immunoprecipitation. The present study demonstrated that HOXC10 and MTFR2 mRNA and protein expression levels were significantly upregulated in CRC tissues and cells. MTFR2 knockdown significantly inhibited CRC cell proliferation, clone formation, invasion and migration. Furthermore, HOXC10 was shown to interact with MTFR2. HOXC10 overexpression was able to significantly reverse the inhibitory effects of MTFR2 knockdown on CRC cells. In conclusion, HOXC10 overexpression activated MTFR2 expression to enhance the proliferation, clone formation, invasion and migration of CRC cells.

Cross-reactivity between MUC1 antigen and MCA: false elevation of serum CA 15-3 level in pregnant and lactating women by Ma695-Ma552-based assay.

PURPOSE: Cancer antigen 153 (CA 15-3) is one of the most commonly used biomarkers of breast cancer. However, elevated CA 15-3 is reported in pregnant and lactating women more frequently on Beckman DxI 800 immunoassay system (Ma695-Ma552 antibody pair) than on Abbott ARCHITECT system (115D8-DF3 antibody pair) in laboratory methodological evaluation. We conducted this study in order to figure out the reason behind this phenomenon. METHODS: Serum CA 15-3 concentration was analyzed in 426 subjects, including 180 patients with breast cancer, 121 patients with benign breast disease, and 125 healthy volunteers (45 pregnant and 80 non-pregnant women). CA 15-3 assay was further validated using another cohort of 112 pregnant or postpartum women. Immunological cross reaction was analyzed by Western blotting and immunoprecipitation. RESULTS: The serum CA 15-3 level was abnormally higher in almost 95% of the pregnant and lactating women detected using Ma695-Ma552 antibody pair (median: 71.4 U/mL) than that detected using 115D8-DF3 antibody pair (median: 16.5 U/mL). Western blotting and immunoprecipitation indicated that such a significant difference was mainly due to the cross reaction between monoclonal antibody Ma552 and mucin-like carcinoma-associated antigen (MCA). CONCLUSIONS: The CA 15-3 assay using 115D8-DF3 antibody pair is more suitable for monitoring therapy in pregnancy-associated breast cancer.

Increased PTPRA expression leads to poor prognosis through c-Src activation and G1 phase progression in squamous cell lung cancer.

PTPRA is reported to be involved in cancer development and progression through activating the Src family kinase (SFK) signaling pathways, however, the roles of PTPRA in the squamous cell lung cancer (SCC) development are unclear. The purpose of this study was to clarify the clinical relevance and biological roles of PTPRA in SCC. We found that PTPRA was upregulated in squamous cell lung cancer compared to matched normal tissues at the mRNA (N=20, P=0.004) and protein expression levels (N=75, P<0.001). Notably, high mRNA level of PTPRA was significantly correlated with poorer prognosis in 675 SCC patients from the Kaplan-Meier plotter database. With 75 cases, we found that PTPRA protein expression was significantly correlated with tumor size (P=0.002), lymph node metastasis (P=0.008), depth of tumor invasion (P<0.001) and clinical stage (P<0.001). The Kaplan-Meier plot suggested that high expression of PTPRA had poorer overall survival in SCC patients (P=0.009). Multivariate Cox regression analysis suggested that PTPRA expression was an independent prognostic factor in SCC patients. In the cellular models, PTPRA promotes SCC cell proliferation through modulating Src activation as well as cell cycle progression. In conclusion, higher PTPRA level was associated with worse prognosis of SCC patients and PTPRA could promote the cell cycle progression through stimulating the c-Src signaling pathways.