NAP1L1: A Novel Human Colorectal Cancer Biomarker Derived From Animal Models of Apc Inactivation

Cui

et al. 2021

Preprint

Background：Breast cancer is the top cancer in women in the world. However, its pathogenesis is still to be determined. The role and molecular mechanism of NAP1L1 in breast cancer have not been reported. Elucidation of molecular mechanism might provide a novel therapeutic target for glioma treatment.Methods：A bioinformatics analysis was conducted to determine the differential expression of NAP1L1 in breast cancer and find the potential biomarker that interacts with NAP1L1 and HDGF. The expression of NAP1L1 in tissues was detected by using immunohistochemistry. Breast cancer cells were transfected with the corresponding lentiviral particles and siRNA. Then, MTT, Edu, plate clone formation, and subcutaneous tumorigenesis in nude mice were used to detect the cell proliferation in breast cancer. Furthermore, coimmunoprecipitation (Co-IP) assay and confocal microscopy were performed to explore the detailed molecular mechanism of NAP1L1 in breast cancer.Results：In this study, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) protein was upregulated based on the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Consistent with the prediction, immunohistochemistry staining showed that NAP1L1 protein expression was significantly increased in breast cancer tissues. Its elevated expression was an unfavorable factor for breast cancer clinical progression and poor prognosis. Stably or transiently knocking down NAP1L1 reduced the cell growth in vivo and in vitro via repressing the cell cycle signal in breast cancer. Furthermore, the molecular basis of NAP1L1-induced cell cycle signal was further studied. NAP1L1 interacted with the hepatoma-derived growth factor (HDGF), an oncogenic factor for tumors, and the latter subsequently recruited the key oncogenic transcription factor c-Jun, which finally induced the expression of cell cycle promoter CCND1 and thus the cell growth of breast cancer. Conclusions：Our data demonstrated that NAP1L1 functions as a potential oncogene via interacting with HDGF to recruit c-Jun in breast cancer.

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NAP1L1 Interacts with Hepatoma-Derived Growth Factor to Recruit C-Jun Inducing Breast Cancer Growth

Liu

Cui

et al. 2021

Preprint

“…NAP1L1 participates in the miR-532-5p-mediated suppression of renal cancer cell proliferation. In colorectal cancer and pancreatic neuroendocrine neoplasm, NAP1L1 was found to be a biomarker, involved in the pathogenesis of these two types of cancers (Schimmack et al, 2014;Zhai et al, 2018;Queiroz et al, 2020). In HCC, NAP1L1 acts as a tumor promoter and is repressed by PRDM8 and let-7c-5p.…”

Section: Discussionmentioning

confidence: 99%

“…NAP1L1 belongs to the human counterpart of the yeast NAP-I protein, a histone-binding factor involved in the cumulative nucleosome formation. NAP1L1 has been shown as a potential tumor promoter and participates in the pathogenesis of several tumors including colorectal cancer, renal cancer, and pancreatic neuroendocrine neoplasm (Schimmack et al, 2014;Zhai et al, 2018;Queiroz et al, 2020). Recent studies on HCC showed that PRDM8 suppresses the occurrence of tumor via interacting with NAP1L1 (Chen et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

NAP1L1 Functions as a Tumor Promoter via Recruiting Hepatoma-Derived Growth Factor/c-Jun Signal in Hepatocellular Carcinoma

Chen

et al. 2021

Front. Cell Dev. Biol.

NAP1L1 has been reported to be significantly involved in the carcinogenesis of hepatocellular carcinoma (HCC). Yet, its detailed molecular basis is still to be determined. Based on the analysis of The Cancer Genome Atlas (TCGA) database, NAP1L1 mRNA was found to be upregulated and predicted the poor prognosis initially. Subsequently, consistent with the prediction, the upregulated expression of NAP1L1 mRNA and protein levels was confirmed by quantitative polymerase chain reaction (qPCR), Western blot, and immunohistochemistry assays. Upregulated NAP1L1 protein positively promoted the disease progression and poor prognosis of HCC. In addition, NAP1L1 protein expression was considered as an independent prognostic factor in HCC. Inhibition of NAP1L1 expression by siRNA or shRNA pathway significantly reduced the cell proliferation and cell cycle transformation in vitro and in vivo. Mechanism analysis first showed that the function of NAP1L1 was to recruit hepatoma-derived growth factor (HDGF), an oncogene candidate widely documented in tumors. Furthermore, the latter interacted with c-Jun, a key oncogenic transcription factor that can induce the expression of cell cycle factors and thus stimulate the cell growth in HCC. Finally, transfecting HDGF or c-Jun could reverse the suppressive effects on HCC growth in NAP1L1-suppressed HCC cells. Our data indicate that NAP1L1 is a potential oncogene and acts via recruiting HDGF/c-Jun in HCC.

NAP1L1 is a novel microtubule‐associated protein

Peng

et al. 2023

Cytoskeleton

Microtubule‐associated proteins (MAPs) regulate assembly and stability of microtubules (MTs) during cell cytokinesis, cell migration, neuronal growth, axon guidance, and synapse formation. Using data mining of the Human Protein Atlas database and experimental screening, we identified nucleosome assembly protein 1 like 1 (NAP1L1) as a new MAP. The Human Protein Atlas and PubMed database screening identified 99 potential new MAPs. Twenty candidate proteins that highly co‐localized with MTs were exogenously expressed with green fluorescent protein (GFP) or hemagglutinin (HA) tags in tissue culture cells and MTs were co‐stained for immunofluorescent microscopy. We found that NAP1L1 is mainly localized in the cytosol with MTs during interphase. Using bacterially expressed recombinant NAP1L1 fragments and purified MTs, we biochemically mapped the MT‐binding site on the N‐terminal region (1–72aa) and the central region (164–269aa) of NAP1L1. NAP1L1 dimerizes through the long helix region (73–163aa), and full‐length NAP1L1 induces the formation of thick MTs, indicating that NAP1L1 has the ability to bundle MTs in cells. Analysis of publicly available RNA‐seq data of NAP1L1 depleted cells suggested that NAP1L1 is involved in cell adhesion and migration in agreement with the function of NAP1L1 as a MAP.