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Gastric cancer (GC) is among the most fatal cancers in China. MicroRNAs (miRNAs) are versatile regulators during GC development and progression. miR‐491‐5p has been demonstrated to act as a tumor suppressor in several types of cancer. However, the role of miR‐491‐5p in GC metastasis remains unknown. Here, we found that miR‐491‐5p was significantly decreased in GC tissues compared with adjacent non‐cancerous tissues, and low miR‐491‐5p level was associated with large tumor size. Overexpression of miR‐491‐5p significantly suppressed GC cell epithelial‐to‐mesenchymal transition (EMT) and tumor metastasis in vitro and in vivo. Mechanistically, SNAIL was identified as a direct target of miR‐491‐5p. The silencing of SNAIL phenocopied the tumor suppressive function of miR‐491‐5p, whereas re‐expression of SNAIL in GC cells rescued the EMT markers and cell migratory ability that were inhibited by miR‐491‐5p. In addition, miR‐491‐5p inhibited FGFR4 indirectly. Inhibition of FGFR4 also decreased the SNAIL level and impaired EMT and cell migration. Taken together, these findings indicate that downregulation of miR‐491‐5p promoted GC metastasis by inducing EMT via regulation of SNAIL and FGFR4. miR‐491‐5p is remarkably downregulated in gastric cancer. Restoration of miR‐491‐5p could effectively inhibited tumor growth and metastasis. We discovered that miR‐491‐5p directly targeted SNAIL and indirectly inhibited FGFR4, resulted in suppressed EMT and tumor metastasis.

Gastric cancer is a prevalent and clinically significant gastrointestinal malignancy worldwide. Gastric cancer is characterized by limited treatment efficacy and a high recurrence rate. In this study, we found that LGALS9 was highly expressed in gastric cancer and may contribute to disease progression by modulating the infiltration of CD8+ T cells. Genetic knockout of LGALS9 reversed T cell function, attenuated immunosuppression, and enhanced the cytotoxic activity of T cells to kill gastric cancer cells. Furthermore, miR‐491‐5p was identified as a potential suppressor in gastric cancer. The microRNA miR‐491‐5p regulated T cell‐mediated immunity by targeting and inhibiting LGALS9, which was similar to the effect of LGALS9 knockout. Overall, the key target LGALS9 and its inhibitor miR‐491‐5p represent promising potential for treating gastric cancer. In this study, we found that LGALS9 is highly expressed in gastric cancer and may affect the development of gastric cancer by participating in the infiltration of CD8+ T cells. Knockout of LGALS9 can reverse T cell function and relieve immunosuppression, and enhance the killing effect of T cells on gastric cancer cells. We also found a potential gastric cancer suppressor miR‐491‐5p, which regulates T cell immunity by inhibiting LGALS9, and exhibits a similar effect to LGALS9 knockout. In conclusion, the key target LGALS9 and its inhibitor miR‐491‐5p have the promising potential to be applied in the treatment of gastric cancer.

Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, for the first time in chondrosarcoma cells, we carried out high-throughput functional screening using impedancemetry, and identified five miRNAs with potential antiproliferative or chemosensitive effects on SW1353 chondrosarcoma cells. The cytotoxic effects of miR-342-5p and miR-491-5p were confirmed on three chondrosarcoma cell lines, using functional validation under normoxia and hypoxia. Both miRNAs induced apoptosis and miR-342-5p also induced autophagy. Western blots and luciferase reporter assays identified for the first time Bcl-2 as a direct target of miR-342-5p, and also Bcl-xL as a direct target of both miR-342-5p and miR-491-5p in chondrosarcoma cells. MiR-491-5p also inhibited EGFR expression. Finally, only miR-342-5p induced cell death on a relevant 3D chondrosarcoma organoid model under hypoxia that mimics the in vivo microenvironment. Altogether, our results revealed the tumor suppressive activity of miR-342-5p, and to a lesser extent of miR-491-5p, on chondrosarcoma lines. Through this study, we also confirmed the potential of Bcl-2 family members as therapeutic targets in chondrosarcomas.

Atherosclerosis (AS) is a complex multifactorial and chronic inflammatory vascular disease that contributes to the development of cardiovascular diseases. Abnormal cellular proliferation in human umbilical vein endothelial cells (HUVECs) is a crucial element in AS development. In this study, we investigated the potential role of the long noncoding RNA LINC02381/microRNA (miR)‐491‐5p/transcription factor 7 (TCF7) axis in regulating HUVEC injury in 30 participants suffering from AS and 30 healthy control participants. We established an in vitro model of AS in HUVECs using oxidized low‐density lipoprotein (ox‐LDL), and measured cellular mRNA and protein levels of LINC02381, miR‐491‐5p, and TCF7 in serum samples using reverse transcription‐quantitative polymerase chain reaction and Western blotting assays. We evaluated cell viability, apoptosis, and inflammation using Cell Counting Kit‐8, flow cytometry, and enzyme‐linked immunosorbent assays, respectively. Moreover, we analyzed apoptosis‐related protein expression using western blotting analysis and determined the association between miR‐491‐5p and LINC02381 or TCF7 using dual‐luciferase reporter assay, RNA pull‐down, and rescue experiments. We observed that LINC02381 was elevated, while miR‐491‐5p was downregulated in serum samples from participants with AS and in ox‐LDL‐treated HUVECs. LINC02381 knockdown was protective against HUVEC injury via miR‐491‐5p inhibition, which is its downstream target. Rescue experiments further demonstrated that miR‐491‐5p alleviated HUVEC injury by modulating TCF7. Thus, LINC02381 knockdown ameliorated HUVEC injury by regulating the miR‐491‐5p/TCF7 axis, which provides new insights into AS treatment strategies. The present study aimed to unravel the role of lncRNA LINC02381/miR‐491‐5p/TCF7 axis in regulating HUVECs injury. Results indicated that silencing of LINC02381 ameliorated HUVECs injury by regulating miR‐491‐5p/TCF7 axis, shedding new insights for AS treatment.