Colorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

Background: As a member of the atypical thiol oxidase family, quiescin sulfhydryl oxidase 2 (QSOX2) has been reported to play an important role in several biological processes, but the expression and function of QSOX2 in colorectal cancer (CRC) remains elusive.Methods: The difference of QSOX2 expression, and its relationship with clinicopathological features and prognosis in CRC, was analyzed by bioinformatic analysis and validated by clinical CRC specimen cohort. The functional characterization of QSOX2 was detected via in vitro and vivo experiments in CRC cell lines, while the potential signaling pathways were predicted by Gene Set Enrichment Analysis (GSEA).Results: Our data based on bioinformatical analysis and clinical validation demonstrated that the expression of QSOX2 in CRC tissues was significantly upregulated. Additionally, the chi-square test, logistic regression analysis, and Fisher’s exact test showed that QSOX2 overexpression was significantly correlated with advanced clinicopathological parameters, such as pathological stage and lymph node metastasis. The Kaplan–Meier curves and univariate Cox regression model showed that QSOX2 overexpression predicts poor overall survival (OS) and disease-free survival (DFS) in CRC patients. More importantly, multivariate Cox regression model showed that QSOX2 overexpression could serve as an independent factor for CRC patients. In vitro and vivo data showed that the proliferation and metastasis ability of CRC cells were suppressed on condition of QSOX2 inhibition. In addition, GSEA showed that the QSOX2 high expression phenotype has enriched multiple potential cancer-related signaling pathways.Conclusion: QSOX2 overexpression is strongly associated with malignant progression and poor oncological outcomes in CRC. QSOX2 might act as a novel biomarker for prognosis prediction and a new target for biotherapy in CRC.

Background: Lamin B2 (LMNB2) is involved in chromatin remodelling and the rupture and reorganization of the nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, there are few reports on the expression and function of LMNB2 in colorectal cancer.Methods: A tissue microarray (TAM) was used to detect the expression of LMNB2 in 226 colorectal cancer tissues and the corresponding adjacent tissues. The CCK-8 colorimetric assay, EdU incorporation analyses, colony formation assays and cell cycle experiments were used to evaluate the effect of LMNB2 on colorectal cancer cell proliferation in vitro, and a mouse tumorigenic model was used to study the effect of LMNB2 on colorectal cancer cells in vivo. The main pathways and genes regulated by LMNB2 were detected by RNA sequencing. Dual-luciferase reporter assays were conducted to test the direct binding between LMNB2 and p21, and ChIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter.Results: The results showed that LMNB2 expression is increased in colorectal cancer tissues. Highly expressed LMNB2 is associated with tumour size and TNM stage. Multivariate Cox analysis showed that LMNB2 can be used as an independent prognostic factor in patients with colorectal cancer. Functional assays indicated that LMNB2 obviously enhanced cell proliferation by promoting cell cycle progression in vitro and in vivo. LMNB2 facilitates cell proliferation via regulating the p21 promoter, whereas LMNB2 had no effect on cell apoptosis in terms of mechanism.Conclusion: LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, indicating the potential value of LMNB2 as a clinical prognostic marker and molecular therapeutic target.

: Recently, an increasing number of biological and clinical reports have demonstrated that imbalance of microbial community has the ability to play important roles among several complex diseases in the level of human health. Having a good knowledge of discovery potential of microbe-disease relationships, which provides the ability to having better understanding on some issues, including disease pathology, further boosts disease diagnostics and prognostics, has been taken into account. Nevertheless, a few of computational approaches can meet the need of huge scale of microbe-disease association discovery. In this work, we proposed the EHAI model, which is Enhanced Human microbe-disease Association Identification. EHAI employed the microbe-disease associations, and then Gaussian interaction profile kernel similarity has been utilized to enhance the basic microbe-disease association. Actually, some known microbe-disease associations and a large amount of associations are still unavailable among the datasets. The ‘super-microbe’ and ‘super-disease’ were employed to enhance the model. Computational results demonstrated that such super-classes have the ability to be helpful to the performance of EHAI. Therefore, it is anticipated that EHAI can be treated as an important biological tool in this field.

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