Anti-PLK1 monoclonal antibody, clone 7D7

Background:Tumor models are critical for our understanding of cancer and the development of cancer therapeutics. The 4T1 murine mammary cancer cell line is one of the most widely used breast cancer models. Here, we present an integrated map of the genome, transcriptome, and immunome of 4T1. Results:We found Trp53 (Tp53) and Pik3g to be mutated. Other frequently mutated genes in breast cancer, including Brca1 and Brca2, are not mutated. For cancer related genes, Nav3, Cenpf, Muc5Ac, Mpp7, Gas1, MageD2, Dusp1, Ros, Polr2a, Rragd, Ros1, and Hoxa9 are mutated. Markers for cell proliferation like Top2a, Birc5, and Mki67 are highly expressed, so are markers for metastasis like Msln, Ect2, and Plk1, which are known to be overexpressed in triple-negative breast cancer (TNBC). TNBC markers are, compared to a mammary gland control sample, lower (Esr1), comparably low (Erbb2), or not expressed at all (Pgr). We also found testis cancer antigen Pbk as well as colon/gastrointestinal cancer antigens Gpa33 and Epcam to be highly expressed. Major histocompatibility complex (MHC) class I is expressed, while MHC class II is not. We identified 505 single nucleotide variations (SNVs) and 20 insertions and deletions (indels). Neoantigens derived from 22 SNVs and one deletion elicited CD8(+)or CD4(+)T cell responses in IFN gamma-ELISpot assays. Twelve high-confidence fusion genes were observed. We did not observe significant downregulation of mismatch repair (MMR) genes or SNVs/indels impairing their function, providing evidence for 6-thioguanine resistance. Effects of the integration of the murine mammary tumor virus were observed at the genome and transcriptome level. Conclusions:4T1 cells share substantial molecular features with human TNBC. As 4T1 is a common model for metastatic tumors, our data supports the rational design of mode-of-action studies for pre-clinical evaluation of targeted immunotherapies.

OBJECTIVE: To clarify the expression pattern of miRNA-875-3p in CRC and its potential regulatory effect on the progression of CRC. MATERIALS AND METHODS: MiRNA-875-3p level in 56 matched CRC tissues and adjacent normal tissues were determined. The correlation between the miRNA-875-3p level and pathological indexes of CRC patients was analyzed. Prognostic potential of miRNA-875-3p in CRC patients was assessed by introducing the Kaplan-Meier curves. Influences of miRNA-875-3p on viability, migration, and wound closure were assessed through a series of functional experiments. The interaction between miRNA-875-3p and PLK1 in regulating the progression of CRC was finally uncovered by Dual-Luciferase reporter gene and rescue experiments. RESULTS: MiRNA-875-3p was downregulated in CRC tissues and cell lines. CRC patients with low level of miRNA-875-3p suffered a higher rate of distant metastasis and worse prognosis. Overexpression of miRNA-875-3p attenuated proliferative and migratory capacities of SW480 and HT29 cells. PLK1 was confirmed to be the target gene of miRNA-875-3p. PLK1 was upregulated in CRC tissues and cell lines, which was negatively regulated by miRNA-875-3p. MiRNA-875-3p alleviated the malignant progression of CRC via negatively regulating PLK1. CONCLUSIONS: MiRNA-875-3p is downregulated in CRC, which is closely related to distant metastasis and poor prognosis of CRC patients. MiRNA-875-3p alleviates the progression of CRC through targeting and downregulating PLK1.