Emerging evidence has identified the critical role of microRNAs in gastric cancer (GC). Herein, this study intends to characterize the tumor suppressive role of microRNA-598 (miR-598) in GC stemlike cells, with the involvement of RRS1. The CD133+ GC stem-like cells were sorted by flow cytometry, after which immunofluorescence assay was used to determine the co-localization of CD133 and CD44v8-10. The miR-598 expression was examined in the CD133+ and CD133-cells. Subsequently, the CD133+ cells were subjected to miR-598 mimics, miR-598 inhibitors or RRS1 siRNA to validate the effect of miR-598 on GC stem-like cell proliferation, colony formation, apoptosis, migration and invasion capacities. Besides, the effect of miR-598 on the expression of key factors (OCT4, SOX2 and NANOG) associated with stem cell characteristics was measured. The obtained results indicated that the sphere forming capacity was higher in CD133+ cells. CD133 + MKN-45 cells expressed CD133 and CD44v8-10, and were expressed on the cell membrane. MiR-598 was poorly expressed in CD133+ cells. Notably, miR-598 negatively regulated RRS1. In response to miR-598 mimics and RRS1 siRNA, the MKN-45 cells displayed inhibited proliferation, colony formation, migration and invasion, accompanied by elevated apoptosis. Besides, the miR-598 inhibitors reversed the situation. This study highlights that miR-598 a tumor suppressor in GC stem-like cells by inhibiting RRS1, whereby miR-598 represses MKN-45 cell growth and invasion by attenuating self-renewal of GC stem-like cells.
Background Recent studies have revealed that long noncoding RNAs (lncRNAs) may hold crucial triggers of the pathogenesis of hematological malignancies, while the studies evaluating the expression pattern of lncRNA in acute myeloid leukemia (AML) are few. Thus, this study aimed to investigate the implication of lncRNA expression pattern in AML development and progression. Methods Bone marrow samples from four AML patients and four controls were subjected to lncRNA sequencing. Then, bone marrow samples from 110 AML patients and 40 controls were proposed to real‐time quantitative polymerase chain reaction (RT‐qPCR) validation for 10 candidate lncRNAs. Clinical data and survival profiles were recorded in AML patients. Furthermore, lncRNA RP4‐576H24.2 expression in AML cell lines and its effect on AML cell proliferation and apoptosis were detected. Results LncRNA expression pattern by sequencing clearly distinguished AML patients from controls, and 630 upregulated and 621 downregulated lncRNAs were identified in AML patients compared to controls, which were mainly enriched in AML oncogene‐related biological process and pathways (such as neutrophil degranulation, leukocyte transendothelial migration, and hematopoietic cell lineage). RT‐qPCR validation observed that six lncRNAs correlated with AML risk, one lncRNA associated with risk stratification, and three lncRNAs correlated with survivals, among which lncRNA RP4‐576H24.2 was the only one correlated with AML susceptibility, risk stratification, and survivals. Further in vitro experiments showed that lncRNA RP4‐576H24.2 was upregulated in AML cell lines compared to normal bone marrow mononuclear cells (BMMCs), and promoted proliferation while inhibited apoptosis in HL‐60 and KG‐1 cells. Conclusions LncRNA expression pattern is closely involved in the development and progression of AML, and several specific lncRNAs exhibit potential to be biomarkers for AML risk and prognosis. Besides, lncRNA RP4‐576H24.2 might be a potential oncogene in AML pathogenesis.
Intrahepatic cholangiocarcinoma (iCCA) derived from epithelial cells of bile ducts is highly aggressive tumor. Hesperidin extracted from citrus fruits is a promising antitumor compound. The purpose of this study is to explore molecular mechanism by which hesperidin affects cholangiocarcinoma progression. Cellular functional experiments were performed and subcutaneous transplant xenograft model was established. Our findings indicated that hesperidin suppressed iCCA cell proliferation in time‐ and concentration‐dependent manners. Hesperidin treatment induced cell cycle arrest at G0/G1 phase, whereas it has no effect on cell apoptosis. Further, data revealed that hesperidin attenuated MEK5 and ERK5 phosphorylation and inhibited ERK5 nuclear localization by reducing MEKK2 activity in MAPK signaling pathway. It could cause alterations in expression of the downstream genes, including CDK4, CDK6 (cell cycle protein kinases), Cyclin D1 (a G1/S checkpoint), P21, and P27 (two G1‐checkpoint CDK inhibitors), thereby arresting cell cycle distribution of iCCA cells in the G0/G1 phase. BIX02189 treatment, a specific inhibitor of MEK5, in combination with hesperidin displayed synergistic inhibitory effects on cell cycle arrest and gene expressions. Furthermore, hesperidin administration alone or in combination with MEK5 inhibitor BIX02189 restrained iCCA tumor growth in vivo. Taken together, these results confirmed that hesperidin regulated the expression of cell cycle‐related genes by inhibiting the activation of MEKK2/MEK5/ERK5 signaling pathway, inducing iCCA cell cycle arrest at the G0/G1 phase. Our study provides a theoretical foundation and experimental basis for further development of hesperidin as a therapeutic agent for iCCA treatment.
We carried out this study to unravel the function of Litchi Seed Aqueous Extracts (LSAE) on biological functions of breast cancer (BC) cells. MTT assay was adopted to measure proliferation of BC cells (MCF7, BT474 and MDA-MB-231) and normal mammary cells (MCF10A) under different time points (24, 48 and 72 h) and different concentrations (50, 100, 200 and 400 μg/mL). MCF-7 cells were selected for subsequent experiments and were grouped into blank group, negative control (NC) group, low-, medium-and high-dose LSAE (L-LSAE, M-LSAE, H-LSAE) groups. Cell viability, invasion, migration and apoptosis were measured by functional assays. Low dosage of LSAE (50 and 100 μg/mL) enhanced proliferation of MCF10A cells, while high dosage of LSAE (200 and 400 μg/mL) suppressed proliferation of MCF10A cells. The proliferation inhibition rate in BT474 and MDA-MB-231cells was increased relative to that in MCF7 cells. MCF-7 cells in the L-LSAE, M-LSAE and H-LSAE groups were rounded and epithelial-like, in which cell survival rate, epithelial-mesenchymal transition (EMT), invasion and migration abilities were reduced versus the blank and NC groups. The tendency in the H-LSAE group was substantially obvious than those in the L-LSAE and M-LSAE groups (both P < 0.05). We found that LSAE is able to inhibit EMT, invasion and migration in BC cells based on concentration and time.
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