Background:
Recently, a novel crosstalk between non-coding RNAs (ncRNAs) has been casted. However, this has been seldomly investigated in metastatic BC (mBC). H19 and miR-486-5p role in mBC is controversial. ICAM-1 is a recently recognized metastatic engine in mBC. Natural compounds were recently found to alter ncRNAs/target circuits. Yet, Hesperitin modulatory role in altering such circuits has never been investigated in mBC.
Objective:
The aim of this study is to investigate the impact of hesperitin on miR-486-5p/H19/ICAM-1 axis
Methodology:
BC patients (n=20) were recruited in the study. Bioinformatic analysis was performed using different prediction softwares. MDA-MB-231 and MCF-7 cells were cultured and transfected using several oligonucleotides or treated with serial dilutions of hesperitin. RNA was extracted and gene expression analysis was performed using q-RT-PCR. ICAM-1 protein levels were assessed using human ICAM-1 Elisa Kit. Cytotoxic potential of hesperitin against normal cells was assessed by LDH assay. Several functional analysis experiments were performed such as MTT, colony forming and migration assays.
Results:
The study showed that miR-486-5p and H19 has a paradoxical expression profiles in mBC patients. miR-486-5p mimics and H19 siRNAs repressed ICAM-1 and halted mBC hallmarks. A novel crosstalk between miR-486-5p and H19 was observed highlighting a bi-directional relationship between them. Hesperetin restored the expression of miR-486-5p, inhibited H19 lncRNA and ICAM-1 expression and selectively regressed mBC cell aggressiveness.
Conclusion:
miR-486-5p and H19 are inter-connected upstream regulators for ICAM-1 building up miR-486-5p/H19/ICAM-1 axis that has been successfully tuned in mBC cells by hesperitin
Furthermore, we measured cytokine profiles of sera from 6 PDAC patients with elevated CSTA concentration in sera and 9 PDAC patients without elevation. We also examined the expression of CSTA, its substrate, cathepsin B, and cytokines, in tumor tissues in 20 surgically resected PDAC tissues by immunohistochemical staining. Results: We observed increment of CSTA mRNA expression in CD4þ cells of peripheral blood of 41 patients with PDAC compared with that in 20 healthy volunteers. Correspondingly, serum CSTA concentrations in 36 patients with PDAC were higher than those in 37 healthy volunteers, and this increase was correlated with PDAC clinical stage. We found that IFN-g, TNF-a, and IL-1b concentrations in sera were significantly correlated with those of CSTA in sera of PDAC patients. As for tumor tissue analysis, CSTA expression was detected in some tumor tissues and many tumor-infiltrating immune cells, particularly neutrophils. Cathepsin B expression was observed in most tumor tissues and tumor-infiltrating immune cells, particularly macrophages. Conclusions: CSTA expression was involved in the PDAC inflammatory condition in local tumor microenvironment. The CSTA concentration in peripheral blood of PDAC patients have a possibility of potential role as a PDAC immunopathological biomarker.
without intermediate cell foci. Two monoclonal cases showed histologically ambiguous border between HCC and CC components with more intermingled pattern than biclonal cases. Conclusions: We compared genetic compositions of HCC and CC components and matched clonality with histologic feature in cHCC-CC using targeted sequencing. Two (50%) of four cases had different clones between HCC and CC components with more distinguished histologic features than monoclonal cases. Considering such heterogeneity, partly sequencing is recommended for cHCC-CC, especially in those who have histologically distinguished HCC and CC components regardless of the presence of intermediate component.Legal entity responsible for the study: Nara Yoon. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.85P The role of topoisomerase II-a (TOPO IIA) as a predictive factor for response to neoadjuvant anthracycline-based chemotherapy in locally advanced breast cancer
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