Search

Increasing lines of evidence indicate the role of long non-coding RNAs (LncRNAs) in gene regulation and tumor development. Hence, it is important to elucidate the mechanisms of LncRNAs underlying the proliferation, metastasis, and invasion of lung adenocarcinoma (LUAD). We employed microarrays to screen LncRNAs in LUAD tissues with and without lymph node metastasis and revealed their effects on LUAD. Among them, Linc00426 was selected for further exploration in its expression, the biological significance, and the underlying molecular mechanisms. Linc00426 exhibits ectopic expression in LUAD tissues and cells. The ectopic expression has been clinically linked to tumor size, lymphatic metastasis, and tumor differentiation of patients with LUAD. The deregulation of Linc00426 contributes to a notable impairment in proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the deregulation of Linc00426 could reduce cytoskeleton rearrangement and matrix metalloproteinase expression. Meanwhile, decreasing the level of Linc00426 or increasing miR-455-5p could down-regulate the level of UBE2V1. Thus, Linc00426 may act as a competing endogenous RNA (ceRNA) to abate miR-455-5p-dependent UBE2V1 reduction. We conclude that Linc00426 accelerates LUAD progression by acting as a molecular sponge to regulate miR-455-5p, and may be a potential novel tumor marker for LUAD.

Background: microRNAs (miRNAs) have been verified as molecular targets for regulating tumor proliferation, invasion, and metastasis in tumor progression. However, the relationship between miRNAs and cellular energy metabolism in breast cancer still needs to be clarified. This study aimed to investigate the role of miR-429 in breast cancer progression., Methods: Bioinformatic analyses were employed to detect the relationship between miR-429 and cancer-related signaling pathways. We used a Kaplan-Meier curve to analyze survival rate in patients with high or low expression of miR-429. We used real-time quantitative PCR (RT-qPCR) to detect the expression of miR-429 in different cell lines. Sh-con, over-miR-429, miR-429 inhibitor, and sh-inhibitor control were transfected. Colony formation and EDU assay were used to detect the proliferation of transfected cells. Wound healing and transwell assays were performed to detect the mobility and invasion ability of transfected cells. Western blot assay was used to detect relative protein expression in transfected cells and different tissues. Bioinformatic analyses were conducted to detect the target proteins expression in different breast cancer databases. Dual luciferase reporter assay was used to confirm the binding site between miR-429 and fibronectin 1 (FN1)., Results: The results of our study indicate that MiR-429 and its target genes are associated with cancer-related signaling pathways and that higher miR-429 expression corresponds with a better prognosis. When miR-429 was overexpressed, the proliferation, invasion of MDA-MB-231 were inhibited. MiR-429 was able to suppress the Wnt/β-catenin signaling pathway, and FN1 overexpression could rescue the influence of over-miR-429., Conclusions: The results of our study suggest that miR-429 suppresses the proliferation and invasion of breast cancer via inhibiting the Wnt/β-catenin signaling pathway., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objective To investigate the molecular mechanism by which miR-93-5p promotes the invasion and migration of triple negative breast cancer (TNBC) cells. Methods The miR-93-5p and faciogenital dysplasia-5 (FGD5) were screened out by Gene Expression Omnibus (GEO). Bioinformatics software was used to predict the candidate target genes for miR-93-5p. The relative expression of miR-93-5p in cells was detected by real-time quantitative PCR. Western blot was used to detect the relative expression of FGD5. Transwell TM assay was performed to detect the effects of miR-93-5p on the invasion and migration of MDA-MB-231 cells. The expression of FGD5 and survival curve in breast cancer and the correlation between miR-93-5p and FGD5 were analyzed by bioinformatics database. Dual luciferase reporter gene experiment was employed to verify the targeting relationship between miR-93-5p and FGD5. Results The miR-93-5p was highly expressed in TNBC tissues and cell lines. The higher the expression of miR-93-5p was, the worse the prognosis of breast cancer patients were. Knockdown of miR-93-5p inhibited the invasion and migration ability of MDA-MB-231 cells. Bioinformatics analysis showed that there were complementary sequences between miR-93-5p and FGD5. FGD5 presented low expression in breast cancer tissues and lower FGD5 expression in breast cancer patients corresponded to poorer prognosis. The expression levels between miR-93-5p and FGD5 were negatively correlated. Transfection of miR-93-5p inhibitor plasmid up-regulated the expression of FGD5 in TNBC cells. Dual luciferase reporter gene experiments confirmed that miR-93-5p could down-regulate the luciferase activity of wild-type FGD5. Conclusion The miR-93-5p can promote the invasion and migration of TNBC cells by targeting FGD5.

Objective: To investigate the effect of miR-204 on the invasion and metastasis of breast cancer by targeted regulation of HNRNPA2B1., Methods: The bioinformatics database was used to obtain data of the expressions of miR-204 in breast cancer patients and the survival rate of the patients. RT-qPCR was used to detect the expression of miR-204 in breast cancer cell lines. The expression vector GV369-miR-204 was used to overexpress miR-204 in MDA-MB-231 cells. Transwell assay was performed to detect the effect of miR-204 on the migration and invasion ability of the breast cancer cells. The key genes (hub genes) of miR-204 were determined by bioinformatics method. A dual luciferase assay was used to analyze the targeting relationship between miR-204 and HNRNPA2B1. The expression of HNRNPA2B1 in MDA-MB-231 cells after miR-204 overexpression was detected by Western blotting, and Transwell assay was used to examine the changes in the cell invasion ability., Results: The expression of miR-204 was decreased in both breast cancer tissues, and was significantly lower in breast cancer MDA-MB-231 cells than in MCF-10A cells ( P < 0.05). The decreased expression of miR-204 was associated with poorer prognosis of breast cancer patients ( P < 0.05). Upregulation of miR-204 in MDA-MB-231 cells significantly inhibited the invasion and migration of the cells ( P < 0.05). Analysis of the data from the Starbase revealed that the expression of miR-204-5p was negatively correlated with the expression of HNRNPA2B1, and the expression of HNRNPA2B1 was increased in breast cancer patients ( P < 0.05) in association with a poorer prognosis of the patients ( P < 0.05). Dual luciferase assay demonstrated that miR-204 could bind to HNRNPA2B1 in a target-specific manner. Western blotting and Transwell assay showed that miR-204 significant inhibited the migration and invasion ability of breast cancer cells by targeting HNRNPA2B1 ( P < 0.05)., Conclusions: miR-204 expression is decreased in breast cancer tissues and cells, and its overexpression can inhibit the invasion and metastasis of breast cancer cells by targeted regulation of HNRNPA2B1.