Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway.

BACKGROUND: Heterogeneous ribonucleoprotein A1 (hnRNPA1) has been reported to enhance the Warburg effect and promote colon cancer (CC) cell proliferation, but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated. AIM: To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway. METHODS: Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b. The relationship between the expression values and the clinicopathological features of the patients was investigated. Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction, while differences in protein expression were analyzed using western blot. Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays, and cell cycle and apoptosis were detected using flow cytometric assays. The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay. The Warburg effect was evaluated by glucose uptake and lactic acid production assays. RESULTS: The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls (P < 0.05). Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC, including stage I, II-III, and IV. Furthermore, the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification. HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway, thereby promoting proliferation of HCT116 and SW620 cells. However, the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b, effectively blocking the Warburg effect. CONCLUSION: These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer.

Chemokine-like factor (CKLF)-like, MAL and related proteins for vesicle trafficking and membrane link (MARVEL) transmembrane domain-containing family proteins (CMTMs) have significant roles in the immune system, in male reproduction, as well as in tumorigenesis. Previous studies have shown that CMTM family member 7 (CMTM7) was broadly expressed in various normal tissues, but not in lung, gastric, esophageal, pancreas, and cervix cancers. To explore its relationship with liver cancer, we examined the expression of CMTM7 in liver cancers and its correlation with clinical and pathological conditions. We found that CMTM7 expression was markedly reduced in liver cancer tissues, and negatively correlated with TNM staging and tumor metastasis. In vitro studies showed that enforced expression of CMTM7 inhibited the cell growth and migration of liver cancer cells. Further analysis revealed that CMTM7 suppressed AKT signaling and induced cell cycle arrest at the G0/G1 phase in the liver cancer cells, likely as the consequent of decreased levels of cyclin D1, cyclin-dependent kinase 4 (CDK4), and CDK6, and increased p27 expression. Thus, CMTM7 functions as a tumor suppressor in liver cancer through suppressing cell cycle progression.

Metabolomics study of hematopoietic function of Angelica sinensis on blood deficiency mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (AS) has been used in traditional Chinese medicine for thousands of years to enrich and invigorate blood. In this study, the aim is to investigate the influence of AS on metabolism of blood deficiency mice model and to explore its anti-blood deficiency mechanism. MATERIALS AND METHODS: The blood deficiency mice model was induced by being hypodermically injected with N-acetyl phenylhydrazine (APH) and being intraperitoneally injected with cyclophosphamide (CTX). Gas chromatography-mass spectrometry (GC-MS), principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to identify potential biomarkers in plasma and splenic tissue. RESULTS: The levels of white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and platelet (PLT) showed a trend to return to control group after administrating with AS, while the dose of 10g/kg showed the best effect. Potential metabolite biomarkers (nine in the plasma and nine in the spleen homogenates) were identified in this study. These biomarkers were mainly related to five metabolic pathways, such as arachidonic acid metabolism, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, arginine and proline metabolism and TCA cycle. CONCLUSION: Metabolomics was used to reflect an organism׳s physiological and metabolic state comprehensively, indicating that metabolomics was a potentially powerful tool to reveal the anti-blood deficiency mechanism of AS.

[Comparative metabonomics study on urine in rat treated by Angelica sinensis volatile oil].

Metabonomics was employed to investigate the effect of Angelica sinensis volatile oil (ASVO) to the endogenous metabolites of normal rats, and to reveal the possible ways of metabolism in rats caused by ASVO. The fifty male Waster rats were randomly divided into five groups (each consists of 10 rats), such as control group, high dose group of ASVO, middle dose group of ASVO, low dose group of ASVO, and Aspirin group. They were given 0.9% saline, 0.352 mL x kg(-1) ASVO, 0.176 mL x kg(-1) ASVO, 0.088 mL x kg(-1) ASVO and ASP respectively with the equal volume of 0.2 mL. Drugs and vehicle were given for 3 successive days. The urine was collected at 12, 24, 36, 48 h after modeling with metabolic cages. Rat urine metabolic fingerprint in different stages was analyzed using GC-MS, based on which the principal component analysis (PCA)and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were established for metabonomic analysis. Potential biomarkers were screened by using variable importance in the projection (VIP) and T test. It was revealed that the middle dose of ASVO at 36 h induces a substantial change in rat urine. Compared with control group, seven kinds of endogenous metabolites in ASP group and ASVO group change significantly (P < 0.05), among which aconitic acid, succinic acid, citric acid, alpha-ketone glutaric acid, glycine and malic acid content had an upward trend (P < 0.05) and prostaglandin content had a downward trend (P < 0.01). The mechanism of ASVO and ASP have the similarity. It is likely that ASVO intervenes the metabolic process by affecting the energy, amino acid and lipid metabolism. Our work also indicates that rats administrated with ASVO can increase the energy metabolism of the body, induce the production of inflammatory substances and strengthen the body's immune ability. The result has also provide a proof for futher interpret ASVO pharmacological effects.