Structural maintenance of chromosome 4 (SMC4) is associated with tumorigenesis. The present study aimed at detecting SMC4 expression in primary liver cancer and its association with clinicopathological patient data. A total of 72 primary liver cancer tissues and 6 liver cell lines were assessed for expression of SMC4 mRNA and protein with qRT-PCR, western blotting and immunohistochemistry, respectively. SMC4 siRNAs were constructed to knockdown SMC4 expression, and phenotypic changes of hepatocellular carcinoma (HCC) cells were analyzed using flow cytometry and cell viability assays. The data showed that SMC4 mRNA and protein were highly expressed in HCC tissues compared to the normal tissues. Immunohistochemical analysis revealed that 52 of 72 (72.2%) paraffin-embedded primary liver cancer tissues displayed strong cytoplasmic staining of SMC4 protein, whereas only 6 (8.3%) normal liver tissues showed immunostaining of SMC4. Statistical analysis showed that SMC4 expression was significantly associated with tumor size, de-differentiation, advanced stages and vascular invasion of the primary liver cancers. Moreover, knockdown of SMC4 expression reduced HCC cell proliferation. These data demonstrated that expression of SMC4 protein may be useful for the early detection and prediction of primary liver cancer progression.

The data from the current study demonstrated the association of these two DNA repair gene polymorphisms with HCC risk. Future studies will confirm these data before they can be used as a biomarker for assessing HCC risk.

MicroRNAs (miRNAs) play important roles in the regulation of various tumor biological processes including proliferation and apoptosis. MiR-377 has been implicated in many types of cancer, whereas its expressional feature and potential biological function in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we scanned the global miRNA expression profiles in PDAC from The Cancer Genome Atlas (TCGA) and found miR-377 was down-regulated significantly in PDAC. Then, its expression was measured in both pancreatic cancer tissues and cells; the data showed that miR-377 was de-regulated and inversely correlated with pathologic parameters of tumor growth or metastasis. We generated PDAC cell lines with stable overexpression or inhibition of miR-377, and our results indicated that miR-377 up-regulation significantly promoted cell viability, proliferation, and migration in PDAC cells, and also induced cell apoptosis and cell cycle arrest simultaneously. Binding-site predictions by bioinformatics showed that Pim-3 might be a potential target of miR-377. Luciferase reporter assay ulteriorly identified that miR-377 suppressed Pim-3 expression by binding the 3'-UTR. In tumor tissues, we also showed that the Pim-3 expression was inversely correlated with that of miR-377. Furthermore, stable ectopic miR-377 expression in pancreatic cancer cell lines suppressed Pim-3 expression, leading to the attenuation of Bad phosphorylation level at its Ser and promoting cell apoptosis. Overall, these results reveal that miR-377 may have tumor growth suppression function by down-regulating Pim-3 kinase expression to inhibit both pancreatic tumor growth and migration, and induce cell apoptosis. Hence, miR-377 may be a potential diagnostic marker and therapeutic target.

Liver regeneration, an orchestrated process, is the primary compensatory mechanism following liver injury caused by various factors. The process of liver regeneration consists of three stages: Initiation, proliferation and termination. Proliferation‑promoting factors, which stimulate the recovery of mitosis in quiescent hepatocytes, are essential in the initiation and proliferation steps of liver regeneration. Proliferation‑promoting factors act as the 'motor' of liver regeneration, whereas proliferation inhibitors arrest cell proliferation when the remnant liver reaches a suitable size. Certain proliferation inhibitors are also expressed and activated in the first two steps of liver regeneration. Anti‑proliferation factors, acting as a 'brake', control the speed of proliferation and determine the terminal point of liver regeneration. Furthermore, anti‑proliferation factors function as a 'steering‑wheel', ensuring that the regeneration process proceeds in the right direction by preventing proliferation in the wrong direction, as occurs in oncogenesis. Therefore, proliferation inhibitors to ensure safe and stable liver regeneration are as important as proliferation‑promoting factors. Cytokines, including transforming growth factor‑β and interleukin‑1, and tumor suppressor genes, including p53 and p21, are important members of the proliferation inhibitor family in liver regeneration. Certain anti‑proliferation factors are involved in the process of gene expression and protein modification. The suppression of liver regeneration led by metabolism, hormone activity and pathological performance have been reviewed previously. However, less is known regarding the proliferation inhibitors of liver regeneration and further investigations are required. Detailed information regarding the majority of known anti‑proliferation signaling pathways also remains fragmented. The present review aimed to understand the signalling pathways that inhbit proliferation in the process of liver regeneration.

Supplementary Figure 4. AXIN2 RNA expression in b-catenin S37F and K335I knock-in clones. The top panels show the AXIN2 expression levels determined by qRT-PCR (mean ± standard deviation, n ¼ 5) for all analyzed clones. The bottom panels show the results for K335I knock-in clones only. All expression levels are depicted relative to the housekeeping gene GAPDH. Data are presented as mean ± standard deviation. **P < .01; ***P < .001; ****P < .0001. CTR, control. March 2020 Armadillo Repeat 5/6 Mutations of b-Catenin 1043.e6 IgG, immunoglobulin G.