ANP32B promotes colorectal cancer cell progression and reduces cell sensitivity to PRAP1 inhibitor through up-regulating HPF1.

ANP32B, a member of the acidic leucine-rich nuclear phosphoprotein 32 family member B, is aberrantly expressed in various cancers, including colorectal cancer. However, the function and mechanism of action of ANP32B in colorectal cancer remain unclear. The present study therefore analyzed the expression of ANP32B and its activity in colorectal cancer patient samples and colorectal cancer cell lines. ANP32B expression was found to be significantly upregulated in colorectal cancer patient samples and cell lines. Upregulation of ANP32B enhanced colorectal cancer cell proliferation and migration, whereas downregulation of ANP32B suppressed colorectal cancer cell proliferation. RNA sequencing analysis of differentially expressed genes in ANP32B silenced colorectal cancer cells showed that histone PARylation factor 1 (HPF1), which protects against DNA damage by interacting with the anti-tumor target PARP1, was significantly downregulated. Luciferase promoter assays testing the regulatory association between ANP32B and HPF1 showed that ANP32B interacted with the HPF1 promoter. Analysis of colorectal cancer samples from The Cancer Genome Atlas showed that ANP32B and HPF1 expression were positively correlated, and recovery assays showed that ANP32B promoted colorectal cancer progression by up-regulating HPF1. Overexpression of ANP32B also reduced the sensitivity of colorectal cancer cells to PARP1 inhibitor, consistent with the oncogenic role of ANP32B. ANP32B may alter the sensitivity of colorectal cancer cells to PARP1 inhibitor via a mechanism associated with the HPF1 gene. In summary, these findings showed that ANP32B acted as a tumor promoter, potentiating both colorectal cancer malignancy and drug resistance. Targeting the ANP32B/HPF1 axis may have benefit for patients with colorectal cancer.

Comparative investigation of the effects of specific antigen­sensitized DC­CIK and DC­CTL cells against B16 melanoma tumor cells.

The use of personalized adoptive immunotherapy as a potential novel approach is promising in the treatment of tumors resistant to conventional therapies. In the present study, dendritic cell (DC)­cytokine­induced killer (CIK) and DC­cytotoxic lymphocyte (CTL) cells were cultured to examine their phenotype, proliferation and cytotoxicity against B16 melanoma tumor cells. In addition, comparative investigations of the effect of specific antigen­sensitized DC­CIK and DC­CTL cells against B16 melanoma tumor cells were performed in vitro and in vivo. The results showed that the phenotypes of the co­cultured cells were altered, and DCs promoted DC­CIK cell and DC­CTL cell differentiation and maturation in vitro. Lactate dehydrogenase cytotoxic analysis indicated that the cytotoxicity increased as the effector to target ratio increased between 10:1 and 40:1, and the cytotoxic effect towards B16 melanoma cells by DC­CTL cells was significantly higher, compared with that of DC­CIK cells. To further examine the antineoplastic efficacy of DC­CIK and DC­CTL cells in vivo, the present study performed tail­intravenous injection of DC­CIK cells and DC­CTL cells, which attenuated B16 melanoma cell­engrafted tumor growth, induced G0/G1 cell cycle arrest and accelerated cell apoptosis. Taken together, these results suggested that the use of DC­CTL or DC­CIK cell therapy as a personalized adoptive immunotherapy may regulate immune status and inhibit tumor growth in vivo. In addition, the experiments indicated that DC­CTL cells offer superior antineoplastic activity, compared with DC­CIK cells against B16 melanoma tumor cells.