Accumulating evidence supports the notion that epigenetic modifiers are abnormal in carcinogenesis and have a fundamental role in cancer progression. Among these aberrant epigenetic modifiers, the function of histone methyltransferase KMT2A in somatic tumors is not well known. By analyzing KMT2A expression in patient tissues, we demonstrated that KMT2A was overexpressed in colorectal cancer tissues in comparison with adjacent normal tissues and its expression was positively correlated with cancer stages. In KMT2A‐knockdown HCT116 and DLD1 cells, cell invasion and migration were consequently suppressed. In addition, KMT2A depletion effectively suppressed cancer metastasis in vivo. Mechanistically, cathepsin Z (CTSZ) was demonstrated to be an important downstream gene of KMT2A. Further studies showed that p65 could recruit KMT2A on the promoter region of the downstream gene CTSZ and knockdown of p65 could reduce the KMT2A on the promoter of CTSZ. Finally, our present study revealed that KMT2A epigenetically promotes cancer progression by targeting CTSZ, which has specific functions in cancer invasion and metastasis.

BackgroundSecreted frizzled-related protein 1 (SFRP1) is a member of the SFRPs family that modulates the Wnt signal transduction pathway. Recent studies have showed down-regulation of SFRP1 expression in colorectal cancer (CRC). We aimed to evaluate the effect of SFRP1 on the proliferation, migration, invasion and apoptosis of CRC cells in vitro.Materials and methodsWe used real-time fluorescence quantification (RT-PCR) and Western blotting to detect SFRP1 expression in CRC, pericarcinomatous tissues and CRC cell lines. We assessed the influence of overexpression and knockdown of SFRP1 on CRC cell proliferation, migration, invasion, and apoptosis, Western blotting was used to evaluate protein levels of Wnt, β-catenin, and apoptosis-related proteins.ResultsThe expression of SFRP1 was significantly decreased in CRC tissues. Among the six CRC cell lines (sw-480, sw1116, caco-2, ht-29, colo-205, and hct-116), RT-PCR revealed that sw1116 cells had the lowest expression of SFRP1, while caco-2 cells had the highest SFRP1 expression. SFRP1 overexpression in sw1116 cells significantly suppressed cell proliferation while SFRP1 knockdown in caco-2 cells significantly increase the cell proliferation. In addition, overexpression of SFRP1 in sw1116 cells remarkedly suppressed cell migration and invasion, whereas knockdown of SFRP1 in caco-2 cells resulted in significant enhancement of migration and invasion. Furthermore, SFRP1 overexpression in sw1116 cells promoted cell apoptosis. Western blotting showed that SFRP1 overexpression significantly decreased the protein levels of Wnt, β-catenin and apoptosis-related proteins, including MMP2, MMP9, Twist, CDK1, TGF, and Bcl2.ConclusionOur results demonstrate that SFRP1 suppresses cell proliferation, migration and invasion, and promotes apoptosis in CRC cells.

ObjectivesThis study aims to find the effect of onion’s extraction on the colorectal cancer with hyperlipidemia.MethodWe established a hyperlipidemia-subcutaneously heterotopic colorectal cancer orthotopic transplant model and fed mice a high fat diet and performing transplantation. Animal models were treated with capecitabine and/or simvastatin and low-, middle-, high- dose of onion’s extraction and both tumor growth rate and blood lipid levels were monitored.ResultsWe found that colorectal cancer in onion’s extraction groups was significantly inhibited, and the effect of high dose of onion’s extraction was equivalent to capecitabine. Onion’s extraction effectively decreased levels of apoB and TC.ConclusionOur study established a hyperlipidemia colon tumor model involving subcutaneous colon translocation and orthotopic transplantation, this model was an ideal research model for mutual influence of hyperlipidemia and colorectal cancer. Onion’s extraction could inhibit the proliferation of colorectal cancer; the function of the high-dose of onion’s extraction was fairly to capecitabine, which provided a new direction in protecting and treating colorectal cancer.

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