Differential expression profile of miRNAs between stable and vulnerable plaques of carotid artery stenosis patients.

Plaque vulnerability is associated with the degree of carotid artery stenosis (CS) and the risk of stroke. MicroRNAs (miRNAs) exert critical functions in disease progression, although only a few miRNAs have been well identified in CS. Therefore, this study aimed to investigate the differential expression profile of miRNAs and their potential functions in plaques of CS patients. Three CS patients with stable plaques and three patients with vulnerable plaques who underwent carotid endarterectomy were enrolled in this study. Differentially expressed miRNAs (DEmiRNAs) between patients with stable and vulnerable plaques were determined using small RNA sequencing. Target genes of DEmiRNAs were predicted and submitted to functional analyses. Validation of dysregulated DEmiRNAs was determined using quantitative real-time polymerase chain reaction (qRT-PCR). After sequencing, 76 DEmiRNAs were identified in vulnerable plaques, including 53 upregulated miRNAs and 23 downregulated miRNAs. Next, 23,495 target genes of the identified DEmiRNAs were predicted and functionally analyzed. This indicated that the target genes of the identified DEmiRNAs were mainly enriched in protein phosphorylation, transcription, nitrogen compound metabolism, endocytosis and autophagy, and related to signaling pathways of Hippo, MAPK, insulin, TGF-ß, FoxO, AMPK and p53. Furthermore, qRT-PCR results for six miRNAs showed that five (83%) of them (hsa-miR-511-5p, hsa-miR-150-5p, hsa-miR-378a-5p, hsa-miR-365b-5p and hsa-miR-6511b-5p) were consistent with the sequencing results. Differential expression profiles and potential function of miRNAs associated with plaque stability in CS patients are identified for the first time, which should help to understand the regulatory mechanism of plaque stability in CS.

RNA Sequencing Reveals the Differentially Expressed circRNAs between Stable and Unstable Carotid Atherosclerotic Plaques.

Objective: This study aimed to identify circular RNA profiles (circRNAs) via high-throughput RNA sequencing and distinguish the differentially expressed (DE) circRNAs between stable and unstable plaques. Methods: RNA sequencing was performed on unstable and stable carotid plaque samples obtained from patients with carotid artery stenosis. DE circRNAs were screened, and six DE circRNAs were verified using quantitative real-time PCR (qRT-PCR). Functional evaluation of the DE circRNAs was conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Results: We screened 344 DE circRNAs in unstable plaques, consisting of 342 upregulated and 2 downregulated circRNAs. GO analysis showed that the host genes of the upregulated circRNAs were related to ER to Golgi transport vesicle membrane, endocytic vesicle membrane, and Ran GTPase binding. KEGG analysis revealed that the host genes of the upregulated circRNAs were primarily associated with protein processing in endoplasmic reticulum, lysine degradation, homologous recombination, epithelial cell signaling in Helicobacter pylori infection, and yersinia infection. The results of qRT-PCR verified three upregulated DE circRNAs and two downregulated DE circRNAs in unstable plaques. Conclusion: Hsa-circ-0001523, hsa-circ-0008950, hsa-circ-0000571, hsa-circ-0001946, and hsa-circ-0000745 may be involved in regulating the stability of atherosclerotic plaques and serves as a therapeutic target for unstable plaques.

Cancer-associated fibroblasts support bone tropic metastasis by acting as coordinators between the tumor microenvironment and bone matrix in breast cancer.

Bone is a common site of metastasis for various types of cancer cells, including breast cancer, and the consequent skeleton-related events observed in patients are severe and often fatal. Currently, it is widely accepted that cancer-associated fibroblasts (CAFs) confer a metastasis-promoting property to breast cancer cells. Furthermore, clinical observations suggest that CAFs mediate the bone tropism of metastatic breast cancer cells. Therefore, a deeper understanding of the mechanism by which CAFs are involved in the bone-tropic metastasis of breast cancer can facilitate the study of the novel and effective therapeutic drugs for the corresponding targets. In this review, we focused on the coordinator role of CAFs in remolding breast cancer cells and remodeling the bone marrow during metastasis. We discussed the potential roles of the CXCL12/CXCR4 axis, the CAFs-CSCs reinforcing loop, and exosomes in this malignant process. In summary, in agreement with Paget's theory, CAFs play a pivotal role in bone colonization by breast cancer cells by providing a "fertile soil" for the "selected seeds" by influencing tumor-intrinsic characteristics and microenvironment (ME).