Lin Lin,Xin Bing,Jiang Tao,Wang Xin-lu,Yang Hua,Shi Tie-mei
Long non-coding RNAs are associated with the pathogenesis of cancers. Moreover, LINC00460 is involved in the development of multiple cancers. However, the function of LINC00460 in cervical cancer (CC) remains inconclusive. Herein, CC tissues and tumor-adjacent tissues were collected from patients. The effect of LINC00460 silencing in cell proliferation and apoptosis in CC was explored in vitro and in vivo. Additionally, the interaction between LINC00460 and miR-503-5p was analyzed using dual luciferase reporter assay. The expression of genes and proteins was assayed using quantitative real-time PCR, western blotting and immunohistochemistry, cell viability using MTT assay, cell cycle distribution using flow cytometry, cell apoptosis using Annexin V staining, Hoechst staining and TUNEL assay. LINC00460 levels in CC tissues were higher than tumor-adjacent tissues. LINC00460 silencing suppressed proliferation and promoted apoptosis of CC cells as evidenced by decreased cell viability, inhibited proliferation-related protein and cell cycle protein expressions and G1/S transition, increased apoptotic cells and Hoechst-positive cells, and enhanced apoptosis-related protein expressions. LINC00460 could bind to miR-503-5p and LINC00460 silencing enhanced miR-503-5p expression and inhibited its target gene expressions in CC cells. MiR-503-5p inhibition reversed LINC00460 silencing-caused inhibition of cell proliferation and miR-503-5p target gene expressions, and promotion of cell apoptosis. LINC00460 silencing also attenuated tumor growth, promoted miR-503-5p levels and cell apoptosis, and inhibited cell proliferation and miR-503-5p target gene expressions in tumor tissues. Hence, LINC00460 functioned as an oncogene in CC that affected cell proliferation and apoptosis via sponging miR-503-5p. This study provides a novel therapeutic target for CC.
Background This study compared the effect of ultrasound microbubble-mediated miR-503–5p downregulation with that of pure liposome-mediated miR-503–5p downregulation on colorectal cancer (CRC) progression and explored the downstream mechanism. Methods Bioinformatics tools were utilized to predict miR-503–5p-targeted genes and CRC progression-associated genes. MiR-503–5p and sal-like 1 (SALL1) expressions in CRC cells and tissues were analyzed by qRT-PCR and/or bioinformatics tools; their correlations with overall survival and clinicopathological features of CRC patients were presented, and their interaction was validated by dual-luciferase reporter assay. CRC cells received ultrasound microbubble-mediated miR-503–5p downregulation and/or liposome-mediated miR-503–5p downregulation or SALL1 silencing. Cell phenotype changes were evaluated by flow cytometry, as well as MTT, Wound healing, Transwell and tube formation assays. E-cadherin, N-cadherin, Vimentin , B-cell lymphoma (Bcl)− 2, Cleaved caspase-3, and SALL1 expressions in cells were analyzed by Western blot . Results Upregulated miR-503–5p in CRC tissues and cells was detected, associated with poorer cell differentiation , easier lymph node metastasis and higher TNM stages, and related to poorer prognoses of CRC patients. Ultrasound microbubble-mediated miR-503–5p downregulation relative to pure liposome-mediated miR-503–5p downregulation better decreased viability, inhibited migration, invasion and tube formation, enhanced apoptosis, upregulated SALL1, E-cadherin and Cleaved caspase-3, and downregulated miR-503–5p, N-cadherin, Vimentin and Bcl-2 in CRC cells. SALL1 was targeted by miR-503–5p, low-expressed in CRC tissues and cells and positively related to CRC patients’ survival. Silencing SALL1 exerted the opposite effects, which reversed the effects of ultrasound microbubble-mediated miR-503–5p downregulation and vice versa. Conclusion Ultrasound microbubble-mediated miR-503–5p downregulation suppressed in vitro CRC progression via promoting SALL1 expression.
危险品化学品经营许可证（带存储）