Long noncoding RNAs (lncRNAs) are implicated in various cancers, including colon cancer. Liver metastasis is the main cause of colon cancer-related death. However, the roles of lncRNAs in colon cancer liver metastasis are still largely unclear. In this study, we identified a novel lncRNA B3GALT5-AS1, which is reduced in colon cancer tissues and further reduced in colon cancer liver metastasis tissues. Reduced expression of B3GALT5-AS1 is associated with liver metastasis and poor outcome of colon cancer patients. Gain-of-function and loss-of-function assays revealed that B3GALT5-AS1 inhibited proliferation but promoted migration and invasion of colon cancer cells. Further investigation revealed that B3GALT5-AS1 directly bound to the promoter of miRNA-203, repressed miR-203 expression, upregulated miR-203 targets ZEB2 and SNAI2, and induced epithelial-to-mesenchymal transition (EMT). In vivo study revealed that B3GALT5-AS1 suppressed colon cancer liver metastasis via its binding on miR-203 promoter and the repression of miR-203. miR-203 is increased and epithelial phenotype is preferred in colon cancer liver metastasis tissues. Collectively, our data revealed the suppressive roles of B3GALT5-AS1/miR-203/EMT regulation axis in colon cancer liver metastasis. Our data suggested that the activating B3GALT5-AS1/miR-203/EMT axis may be potential therapeutic strategy for colon cancer liver metastasis.

Clinical studies have shown that melatonin lowers the frequency of thrombocytopenia in patients with cancer undergoing radiotherapy or chemotherapy. Here, we investigated the mechanisms by which melatonin promotes platelet formation and survival. Our results show that melatonin exerted protective effects on serum-free induced apoptosis of CHRF megakaryocytes (MKs). Melatonin promoted the formation of MK colony forming units (CFUs) in a dose-dependent manner. Using doxorubicin-treated CHRF cells, we found that melatonin rescued G2/M cell cycle arrest and cell apoptosis induced by doxorubicin. The expression of p-AKT was increased by melatonin treatment, an effect that was abolished by melatonin receptor blocker. In addition, we demonstrated that melatonin enhanced the recovery of platelets in an irradiated mouse model. Megakaryopoiesis was largely preserved in melatonin-treated mice. We obtained the same results in vivo from bone marrow histology and CFU-MK formation assays. Melatonin may exert these protective effects by directly stimulating megakaryopoiesis and inhibiting megakaryocyte apoptosis through activation of its receptors and AKT signaling.

In the process of epithelial-mesenchymal transition (EMT), epithelial cancer cells transdifferentiate into mesenchymal-like cells with high motility and aggressiveness, resulting in the spread of tumor cells. Immune cells and inflammation in the tumor microenvironment are the driving factors of EMT, but few studies have explored the core targets of the interaction between EMT and tumor immune cells. We analyzed thousands of cases of gastric cancer and gastric tissue specimens of TCGA, CPTAC, GTEx and analyzing QPCR and IHC data of 56 gastric cancer patients in SYSU Gastric Cancer Research Center. It was known that EMT has an important connection with the infiltration of NK cells, and that the expression of vinculin may be the target of the phenomenon. The increased expression of vinculin is closely related to the aggressiveness and distant metastasis of cancer, which affects the survival prognosis of the patient. Moreover, through in vitro experiments under 3D conditions, we found that vinculin, cell invasion and metastasis are clearly linked. VCL can affect EMT and tumor immunity by regulating EPCAM gene expression. The role and mechanism of action of vinculin have been controversial, but this molecule may downregulate EpCAM (epithelial cellular adhesion molecule) and its own role in gastric cancer through DNA methylation, causing NK cells to enrich into tumor cells and kill tumor cells. At the same time, it promotes the occurrence of EMT, which in turn causes tumor metastasis and thus poorer prognosis.