Search

This study tended to clarify the role of miR‐126 in non‐small cell lung cancer (NSCLC) cell biological behaviors in vitro, containing cell proliferation, migration, invasion, and apoptosis. miRNA expression microarray related to NSCLC was accessed from gene expression omnibus (GEO) database and subjected to differential analysis using the "limma" package. Real‐time quantitative PCR was conducted to assess the expression of miR‐126 in NSCLC cell lines. wIn vitro experiments including 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT), wound healing assay, Transwell, and flow cytometry assay were used for evaluating the effect of miR‐126 on cell proliferation, migration, invasion, and apoptosis. Additionally, target mRNA for miR‐126 was predicted and further validated by bioinformatics analysis and dual‐luciferase reporter assay, respectively. It suggested that miR‐126 was significantly down‐regulated in NSCLS based on the expression microarray, and similar expression trend was exhibited in cancer cell lines. In the meantime, overexpression of miR‐126 was found to result in inhibition of cell proliferation, migration, and invasion while promotion of cell apoptosis, with reductions in protein expression of AKT2 and phosphorylated HK2 (p‐HK2) as well. AKT2, identified to be a direct target of miR‐126 in NSCLC as judged by dual‐luciferase reporter assay. Additionally, overexpression of AKT2 was observed to have the ability of elevating p‐HK2 protein expression and reversing the effect of miR‐126 on NSCLC cell proliferation, migration, and invasion. Given the above findings, we can see that miR‐126 exerts its role in NSCLC cell proliferation, migration, invasion, and apoptosis with the aid of AKT2/HK2 axis. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionIdentifying subtypes of lung adenocarcinoma (LUAD) patients based on mitochondrial energy metabolism and immunotherapy sensitivity is essential for precision cancer treatment.LUAD subtypes were identified using unsupervised consensus clustering, and results were subjected to immune and tumor mutation analyses. DEGs between subtypes were identified by differential analysis. Functional enrichment and PPI network analyses were conducted. Patients were classified into high and low expression groups based on the expression of the top 10 hub genes, and survival analysis was performed. Drugs sensitive to feature genes were screened based on the correlation between hub gene expression and drug IC50 value. qRT-PCR and western blot were used for gene expression detection, and CCK-8 and flow cytometry were for cell viability and apoptosis analysis.Cluster-1 had significantly higher overall survival and a higher degree of immunoinfiltration and immunophenotypic score, but a lower TIDE score, DEPTH score, and TMB. Enrichment analysis showed that pathways and functions of DEGs between two clusters were mainly related to the interaction of receptor ligands with intracellular proteases. High expression of hub genes corresponded to lower patient survival rates. The predicted drugs with high sensitivity to feature genes were CDK1: Ribavirin (0.476), CCNB2: Hydroxyurea (0.474), Chelerythrine (0.470), and KIF11: Ribavirin (0.471). KIF11 and CCNB2 were highly expressed in LUAD cells and promoted cell viability and inhibited cell apoptosis.This study identified two subtypes of LUAD, with cluster-1 being more suitable for immunotherapy. These results provided a reference for the development of precision immunotherapy for LUAD patients. [ABSTRACT FROM AUTHOR]

Recent advancements in the field of endothelial markers of lymphatic vessels and lymphangiogenic factors have shed light on the association between several ocular diseases and ocular nascent lymphatic vessels. The immune privilege of corneal tissue typically limits the formation of lymphatic vessels in a healthy eye. However, vessels in the eyes can potentially undergo lymphangiogenesis and be conditionally activated. It is evident that nascent lymphatic vessels in the eyes contribute to various ocular pathologies. Conversely, lymphatic vessels are present in the corneal limbus, ciliary body, lacrimal glands, optic nerve sheaths, and extraocular muscles, while a lymphatic vasculature-like system exists in the choroid, that can potentially cause several ocular pathologies. Moreover, numerous studies indicate that many ocular diseases can influence or activate nascent lymphatic vessels, ultimately affecting patient prognosis. By understanding the mechanisms underlying the onset, development, and regression of ocular nascent lymphatic vessels, as well as exploring related research on ocular diseases, this article aims to offer novel perspectives for the treatment of such conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Ma, Zhang, Hou and He.)

Purpose: The study aims to explore the regulatory mechanism of miR-129-2-3p underlying esophageal carcinoma (EC) cell progression and generate new ideas for targeted treatment of EC., Methods: Mature miRNA expression data and total RNA sequencing data of EC in the TCGAESCA dataset were utilized to explore differentially expressed miRNAs (DEmiRNAs). StarBase database was then utilized to predict targets of miRNA. MiR-129-2-3p and DNMT3B expression in EC cell lines was assayed through qRT-PCR and Western blot. CCK-8, scratch healing, and transwell assays were conducted to assess the impact of miR-129-2-3p on EC cell phenotypes. In addition, a dual-luciferase assay was completed to identify the binding relationship between DNMT3B and miR-129-2-3p., Results: MiR-129-2-3p was noticeably less expressed in EC cell lines, while DNMT3B was highly expressed. MiR-129-2-3p could bind to DNMT3B. Furthermore, in vitro functional experiments uncovered that overexpressed miR-129-2-3p repressed EC cell progression while further overexpressing DNMT3B would restore the above inhibitory effect., Conclusion: MiR-129-2-3p is a cancer repressor in EC cells, and it could target DNMT3B, thus hampering the progression of EC cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Primarily, Toll-like receptor 9 (TLR9) is a specific receptor for microbial DNA in human immune cells. TLR9 has been found to be a promising target in tumor immunotherapy but the direct effect of its activation on tumor cells remains unknown. In this study, we examined the effect of TLR9 ligation on estrogen receptor alpha (ERalpha)-mediated transactivation of breast cancer. Luciferase report gene assays, RNA interference of TLR9 and Chromatin immunoprecipitation were performed to measure the effect of TLR9 ligation on ERalpha-mediated transactivity of T47D and MCF-7 cells. Bromodeoxyuridine incorporation assay was used to examine the effect of TLR9 ligation on estrogen (E2)-induced proliferation of breast cancer cells. We also investigated the mechanism for the effect of TLR9 ligation on ERalpha-mediated transactivity. We found that ERalpha-mediated transcription via estrogen response element of human breast cancer cells line T47D was significantly suppressed when treated with 17beta-estradiol in combination with TLR9 agonist CpG oligonucleotides and this effect of CpG was dependent on TLR9. Furthermore, nuclear factor kappaB (NF-kappaB) inhibitor BAY 11-7082 could abolish the inhibitory effect of CpG oligonucleotides on ERalpha-mediated transactivation. We also confirmed the effect of CpG oligonucleotides on ERalpha-mediated transactivation in the breast cancer cell line MCF-7 forced to stably overexpress TLR9. Finally, we observed that CpG oligonucleotides were also able to inhibit estrogen-induced proliferation of breast cancer cells as a consequence of decreased ERalpha-mediated transactivation. Taken together, our data suggest that TLR9 signal pathway, by activating NF-kappaB, negatively regulates ERalpha-mediated transactivation of breast cancer. Thus, TLR9 agonist inhibits the proliferation of breast cancer cells in response to estrogen.