The pivotal roles of long noncoding RNAs have been reported in various cancers. Recently, FBXL19-AS1 was proposed to be involved in tumor progression. However, its role in lung adenocarcinoma (LUAD) remains elusive. In this study, we observed that FBXL19-AS1 was significantly upregulated in LUAD tissues and high FBXL19-AS1 expression in LUAD was associated with a poor prognosis. Nevertheless, miR-203-3p showed the opposite effect. Moreover, cell viability and apoptosis analysis revealed that FBXL19-AS1 knockdown could arrest LUAD cells in G0/G1 phase and inhibit cell proliferation, migration and invasion in vitro and inhibited LUAD tumor progress in vivo. Mechanistically, we identified FBXL19-AS1 could act as a miR-203a-3p sponge using dual-luciferase reporter assay. In addition, we demonstrated that downregulation of miR-203a-3p reversed growth inhibition of LUAD cells caused by FBXL19-AS1 knockdown. Finally, FBXL19-AS1/miR-203a-3p axis was found to associate with baculoviral IAP repeat-containing protein 5.1-A-like (survivin), distal-less homeobox 5, E2F transcription factor 1, and zinc finger E-box binding homeobox 2 to regulate metastasis in LUAD cells. This study reveals a significance and mechanism of FBXL19-AS1 in LUAD proliferation and metastasis and offers a potential prognostic marker and a therapeutic target for patients with LUAD.
Objective To explore safe and effective precision management strategies for breast cancer based on Chinese herbal medicine, and to provide evidence for individualized therapy. Methods Lycorine, an alkaloid from Lycoris radiata , was investigated for its anti-breast cancer effects in Michigan cancer foundation (MCF)-7 cells. miRNA high-throughput sequencing was performed to identify differentially expressed miRNAs after lycorine treatment, followed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses to determine key regulatory pathways. The expression of miR-203a-3p and mitogen‑activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway-related proteins was examined by real-time quantitative PCR (qPCR) and Western blotting. Cell proliferation and cell cycle distribution were assessed using cell counting kit-8 (CCK-8) assay and flow cytometry. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between miR-203a-3p and Kirsten rat sarcoma viral oncogene homolog (KRAS). Results The miRNA sequencing demonstrated that lycorine dose-dependently downregulated miR-203a-3p in MCF-7 cells. GO and KEGG analyses identified the MAPK/ERK signaling pathway as the principal pathway involved in lycorine-mediated inhibition of cell proliferation. qPCR and Western blotting confirmed that lycorine reduced the expression of miR-203a-3p and suppressed key components of the MAPK/ERK pathway at both mRNA and protein levels, including KRAS, v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), mitogen-activated protein kinase kinase 1/2 (MEK1/2), ERK1/2, as well as phosphorylated rapidly accelerated fibrosarcoma (p-RAF), p-MEK1/2, and p-ERK1/2. Functional assays showed that lycorine treatment or miR-203a-3p inhibition significantly suppressed MCF-7 cell proliferation and induced M−phase cell cycle arrest, whereas miR-203a-3p overexpression reversed these inhibitory effects. Dual-luciferase reporter assay verified that miR-203a-3p directly targeted KRAS. Hierarchical clustering further demonstrated coordinated regulation of MAPK/ERK pathway-related genes and proteins by lycorine, with high-dose lycorine producing effects comparable to direct miR-203a-3p inhibition. Conclusions The findings imply that miR-203a-3p has potential as a therapeutic target for the treatment of breast cancer. Furthermore, lycorine exerts its anti-tumor effects by modulating the miR-203a-3p/MAPK signaling axis, thereby providing a promising strategy for precision medicine in breast cancer treatment.
Proliferative diabetic retinopathy (PDR) is a common complication of diabetes mellitus, characterized by abnormal retinal angiogenesis. MicroRNA-203-3p (miR-203-3p) was found to be down-regulated in a murine model of proliferative retinopathy. This study was performed to explore the role of miR-203a-3p in retinal angiogenesis of PDR. Firstly, a rat OIR model, which was used to mimic PDR, was established and the OIR rats were treated with scrambled control or miR-203a-3p agomir by intravitreal injection. The results showed that the level of miR-203a-3p was decreased in OIR rats, and forced over-expression of miR-203a-3p inhibited OIR-induced retinal angiogenesis as evidenced by reduced blood vessel profiles and CD31 expression. OIR-induced up-regulation of VEGFA, HIF-α, PCNA, and MMPs in the retina was also counteracted by miR-203a-3p. Additionally, high glucose (HG)-induced proliferation, migration and tube formation of human retinal microvascular endothelial cells (HRMECs) were also dampened by the up-regulation of miR-203a-3p. Dual-luciferase reporter assay showed that miR-203a-3p could specifically bind to the 3′UTR of VEGFA and HIF-1α. Over-expression of VEGFA or HIF-1α restored the tube formation activity of HRMECs suppressed by miR-203a-3p. In conclusion, our findings demonstrate that up-regulation of miR-203a-3p might inhibit pathological retinal angiogenesis of PDR by targeting VEGFA and HIF-1α.
危险品化学品经营许可证（带存储）