Gallstone disease, including cholesterol precipitation in bile, increased bile salt hydrophobicity and gallbladder inflammation. Here, we investigated miRNA and mRNA involved in the formation of gallstones, and explored the molecular mechanisms in the development of gallstones. Differentially expressed 17 miRNAs and 525 mRNA were identified based on Illumina sequencing from gallbladder mucosa of patients with or without gallstones, and were validated by randomly selected 6 miRNAs and 8 genes using quantitative RT-PCR. 114 miRNA target genes were identified, whose functions and regulating pathways were related to gallstones. The differentially expressed genes were enriched upon lipoprotein binding and some metabolic pathways, and differentially expressed miRNAs enriched upon ABC transportation and cancer related pathways. A molecular regulatory network consisting of 17 differentially expressed miRNAs, inclusive of their target genes, was constructed. miR-210 and its potential target gene ATP11A were found to be differentially expressed in both miRNA and mRNA profiles. ATP11A was a direct target of miR-210, which was predicted to regulate the ABC-transporters pathway. The expression levels of ATP11A in the gallstone showed inverse correlation with miR-210 expression, and up-regulation of miR-210 could reduce ATP11A expression in HGBEC. This is the first report that indicates the existence of differences in miRNA and mRNA expression in patients with or without gallstones. Our data shed light on further investigating the mechanisms of gallstone formation.
Breast cancer (BCa) is one of the most lethal malignancies of female reproductive organs. Increasing evidence has revealed that miRNAs participate in both tumorigenesis and multi-drug resistance. MiR-512-3p, a small non-coding RNA (miRNA), was previously found to be upregulated in breast cancer cells. In this study, we first verified that miR-512-3p expression forced a significant reorganization of the tumor architecture, affecting important cellular processes involved in cell-cell contact, cell adhesion and cell motility. Accordingly, induction of miR-512-3p expression significantly enhanced chemosensitivity and decreased metastatic potential in BCa cells. Our study demonstrated that miR-512-3p directly targets the 3'UTR of Livin, thereby decreasing its expression in MCF-7 cells. MiR-512-3p overexpression significantly inhibited breast cancer cell growth and metastasis. Both miR-512-3p overexpression and Livin knockdown significantly increased the chemosensitivity of cancer cells. Epirubicin (EPB), gemcitabine (GCB) and docetaxel (TXT) had antitumor effects in vitro against human breast cancer cell lines, and miR-512-3p overexpression increased tumor sensitivity to these drugs. In addition, miR-512-3p overexpression significantly inhibited tumor growth in vivo. Collectively, our data suggest that miR-512-3p is a significant regulator of tumorigenesis and drug resistance in breast cancer and provides evidence that miR-512-3p may represent a promising target for breast cancer therapy.
BackgroundBreast cancer (BC) is a highly heterogeneous disease, and although immunotherapy has recently increased patient survival in a number of solid and hematologic malignancies, most BC subtypes respond poorly to immune checkpoint blockade therapy (ICB). B cells, particularly those that congregate in tertiary lymphoid structures (TLS), play a significant role in antitumour immunity. However, B‐cell heterogeneity at single‐cell resolution and its clinical significance with TLS in BC need to be explored further.MethodsPrimary tumour lesions and surrounding normal tissues were taken from 14 BC patients, totaling 124,587 cells, for single‐cell transcriptome sequencing and bioinformatics analysis.ResultsBased on the usual markers, the single‐cell transcriptome profiles were classified into various clusters. A thorough single‐cell study was conducted with a focus on tumour‐infiltrating B cells (TIL‐B) and tumour‐associated neutrophils (TAN). TIL‐B was divided into five clusters, and unusual cell types, such as follicular B cells, which are strongly related to immunotherapy efficacy, were identified. In BC, TAN and TIL‐B infiltration are positively correlated, and at the same time, compared with TLS‐high, TAN and TIL‐B in TLS‐low group are significantly positively correlated.ConclusionsIn conclusion, our study highlights the heterogeneity of B cells in BC, explains how B cells and TLS contribute significantly to antitumour immunity at both the single‐cell and clinical level, and offers a straightforward marker for TLS called CD23. These results will offer more pertinent information on the applicability and effectiveness of tumour immunotherapy for BC.
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