Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to compete with microRNAs (miRNAs) in cancer occurrence and development. However, the differential expression of RNAs and their ceRNA network during the development of colon cancer (CC) remains unclear. This study was aimed at comprehensive analysis of the lncRNAs and their ceRNA networks associated with CC. Whole transcriptome sequencing was performed on colorectal and adjacent normal tissues at different pathological stages. Forty-nine lncRNAs were differently expressed between the CC tissues and their adjacent normal tissues at all stages. Aberrant expression of lncRNA CDKN2B-AS1 and lncRNA MIR4435-2HG was confirmed by TCGA database. Moreover, 14 lncRNAs were differentially expressed between early and advance stages of the tumor tissues, and 117 miRNAs were specifically expressed in stage III & IV. Weighted gene co-expression network analysis of 17105 differently expressed mRNAs revealed that the mRNAs shown in module pink, midnight blue, black, and light cyan were related to TNM and pathological stage, and that these mRNAs were enriched in cancer related functions and pathways. As DElncRNA showed a trend of change similar to that of the DEmRNA and opposite to that of DEmiRNA, ceRNA network was constructed with 3 DEmiRNAs, 5 DElncRNAs, and 130 DEmRNAs. Real time PCR revealed that expression of MEG3 was decreased in the tumor tissues belonging to stage III and IV as compared to that in stage I. Moreover, hsa-miR-324-5p was upregulated, while FGFR3, PLCB4, and IKBKB were downregulated in the tumor tissues as compared to that in the adjacent normal tissues. Thus, this study revealed differentially expressed lncRNA between different stages of CC as well as suggested that lncRNA CDKN2B-AS1, MIR4435-2HG, and MEG3 may act as diagnostic biomarkers for the development of CC.
Isoliquiritigenin (ISL), a natural product isolated from licorice root, exhibits anti-gastric cancer effects. However, applications of ISL are still limited in clinical practice due to its poor bioavailability. To discovery of more effective anti-gastric cancer agents based on ISL, aldol condensation reaction was applied to synthesize the ISL analogues. MTS assay was used to evaluate the inhibitory activities of ISL analogues against SGC-7901, BGC-823 and GES-1 cells in vitro. Cell cycle distribution, apoptosis and reactive oxygen species (ROS) generation were detected by flow cytometry. Western blot assay was used to analyze the expression levels of related proteins. The drug-likeness and pharmacokinetic properties were predicted with Osiris property explorer and PreADMET server. As a result, 18 new ISL analogues (ISL-1 to ISL-18) were synthesized. Among these analogues, ISL-17 showed the strongest inhibitory activities against SGC-7901 and BGC-823 cells, and could induce G2/M cell cycle arrest and apoptosis in these two cell lines. Treatment with ISL-17 resulted in increased ROS production and elevated autophagy levels in SGC-7901 cells. The PI3K/AKT/mTOR signaling pathway was down-regulated after treatment with ISL-17 in SGC-7901 cells. The results of drug-likeness and pharmacokinetic prediction indicated that all the ISL analogues complied with Lipinski's rule of five and Veber rule and had a favorable ADME character. Overall, our results attest that ISL-17 holds promise as a candidate agent against gastric cancer.
With the advancement of nanobiotechnology, eco-friendly approaches of plant-mediated silver nanomaterial (AgNP) biosynthesis have become more attractive for biomedical applications. The present study is a report of biosynthesizing AgNPs using Chlorophytum borivilianum L. (Safed musli) callus extract as a novel source of reducing agent. AgNO3 solution challenged with the methanolic callus extract displayed a change in color from yellow to brown owing to the bioreduction reaction. Further, AgNPs were characterized by using UV–visible spectrophotometry, X-ray Diffraction (XRD), Atomic Force Microscopy (AFM), and Fourier Transform Infrared Spectroscopy (FTIR). UV–vis spectrum revealed the surface plasmon resonance property of AgNPs at around 450 nm. XRD pattern with typical peaks indicated the face-centered cubic nature of silver. AFM analysis confirmed the existence of spherical-shaped and well-dispersed AgNPs having an average size of 52.0 nm. Further, FTIR analysis confirmed the involvement of different phytoconstituents of the callus extract role in the process of bioreduction to form nanoparticles. The AgNPs were more efficient in inhibiting the tested pathogenic microbes, namely, Pseudomonas aeruginosa, Bacillus subtilis, Methicillin-resistant Escherichia coli, Staphylococcus aureus, and Candida albicans compared to callus extract. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed the cytotoxic property of AgNPs against human colon adenocarcinoma cell line (HT-29) in a dose-dependent manner. At higher concentrations of 500 μg/mL AgNPs, the cell viability was observed to be only 7% after 24 hours with IC50 value of 254 μg/mL. Therefore, these AgNPs clearly endorse the manifold potential to be used in various biomedical applications in the near future.
Decreased expression of miR-142-3p was observed in human cancers. However, the function and mechanism of miR-142-3p in human colorectal cancer remain obscure. The expressions of miR-142-3p in human colorectal cancer tissues and cell lines were measured by RT-qPCR. The effects of miR-142-3p on cell invasion and migration were detected by transwell assays. The efficiency of aerobic glycolysis was determined by glucose consumption and lactate production. Dual-luciferase reporter assays were performed to confirm the correlation between miR-142-3p and pyruvate kinase isozyme M2 (PKM2). The level of PKM2 was assessed by western blotting. Our results showed that the expression of miR-142-3p was decreased both in human colorectal cancer tissues and in cells. Overexpression of miR-142-3p in cell line attenuated colorectal cancer cell invasion and migration. About the underlying mechanism, we found that miR-142-3p modulated aerobic glycolysis via targeting pyruvate kinase M2 (PKM2). In addition, we demonstrated PKM2 and PKM2-mediated aerobic glycolysis contributes to miR-142-3p-mediated colorectal cancer cell invasion and migration. Hence, these data suggested that miR-142-3p was a potential therapeutic target for the treatment of human colorectal cancer.
Cancer-associated fibroblasts (CAFs) constitute a major component of the tumor microenvironment. CAFs regulated the growth and development, invasion and metastasis of primary tumors, as well as response to treatment. Recent studies indicated that monoclonal antibody therapies had limited success, thus more effective polyclonal antibodies (Poly Abs) is urgently needed. Poly Abs is a possible alternative because they target multiple antigens simultaneously. In this report, we prepared Poly Abs by immunizing rabbits with the bFGF-activated fibroblasts. The Poly Abs inhibited the cancer cells proliferation as revealed by MTT analysis. The Poly Abs induced apoptosis as indicated by flow cytometric analysis, and microscopic observation of apoptotic changes in morphology. Compared with the control IgG, Poly Abs significantly inhibited tumor cells migration as indicated by wound healing and transwell analysis in vitro, and lung metastasis analysis in vivo. Serial intravenous injections of Poly Abs inhibited tumor growth in mice bearing murine CT26 colon carcinoma. Ki67 analysis indicated that Poly Abs significantly inhibited tumor cells proliferation, as compared to control Ig G treatments. Our findings suggested that Poly Abs was an effective agent for apoptosis induction, migration and metastasis inhibition. The Poly Abs may be useful as a safe anticancer agent for cancer immunotherapy in the future.
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