Effects of LINC00894 regulating miR-205-5p/GPNMB axis on proliferation, migration, and invasion of gastric cancer cells
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Abstract:
[Abstract] Objective: To investigate the effects of long intergenic non-coding RNA00894 (LINC00894) on the malignant biological behaviors of gastric cancer (GC) cells via regulating the microRNA-205-5p (miR-205-5p)/glycoprotein non-metastatic melanoma protein B (GPNMB) axis. Methods: Twenty-five pairs of gastric cancer tissues and corresponding adjacent tissues were collected from patients undergoing surgical resection at the First Hospital of Hebei Medical University between November 2022 and September 2023. BGC823 cells were routinely cultured and into control, sh-NC, sh-LINC00894, sh-LINC00894 + anti-NC, and sh-LINC00894+anti miR-205-5p groups, followed by corresponding plasmids transfection using transfection reagents. The mRNA expression of LINC00894, miR-205-5p, and GPNMB in BGC823 cells and cancer tissues of each group was detected using qPCR. Dual luciferase reporter gene assay and AGO2-RNA immunoprecipitation were used to verify the targeted binding relationships between LINC00894 and miR-205-5p, as well as between miR-205-5p and GPNMB. Colony formation assay, EdU staining, wound-healing assay, and Transwell assay were performed to detect cell proliferation, migration and invasion abilities. Western blotting was used to detect the protein expression of CDK1, MMP-2 and MMP-9 in each group of cells. A nude mouse xenograft model was established to determine the effect of LINC00894 knockdown on tumor growth, and immunohistochemistry was used to detect the protein expression of GPNMB in xenograft tissues. Results: LINC00894 and GPNMB were significantly upregulated in gastric cancer tissues and cells,while miR-205-5p was downregulated (both P < 0.05). LINC00894 negatively regulated miR-205-5p, while miR-205-5p negatively regulated GPNMB (all P < 0.05). Knocking down LINC00894 promoted miR-205-5p expression and inhibited GPNMB expression in BGC823 cells (all P < 0.05). Additionally, LINC00894 knockdown suppressed the proliferation, migration and invasion abilities of BGC823 cells, as well as the protein expression of CDK1, MMP-2, and MMP-9 (all P < 0.05). Inhibition of miR-205-5p reversed these effects (all P < 0.05). Knocking down LINC00894 inhibited the growth of BGC823 cell-transplanted tumors, promoted miR-205-5p expression, and inhibited GPNMB protein expression (all P < 0.05). Conclusion: LINC00894 is highly expressed in gastric cancer tissues and cells, while miR-205-5p is downregulated. Knockdown of LINC00894 can regulate the expression of miR-205-5p/GPNMB pathway-related proteins in BGC823 cells, thereby inhibiting their malignant biological behaviors.