Intratumor microbiota: Occult participants in the microenvironment of multiple myeloma.

More recently, microbiota was detected in several tumorous tissues including multiple myeloma (MM), but the roles of which is still under-studied as paucity of research on tumor biology. Moreover, we also detected the presence of microbiota in the bone marrow of patients with MM by 2bRAD-M sequencing technology, which is an incurable hematological malignancy characterized by accumulation of abnormal plasma cells in the bone marrow. However, the roles of intratumor microbiota in tumor disease remains poorly understood. In this review, we critically reviewed recent literature about microbiota in the tumorigenesis and progression of MM. Importantly, we proposed that the emergence of microbiota in the microenvironment of multiple myeloma may be attributed to microbial dysbiosis and impaired intestinal barrier, due to the increased prevalence of MM in patients with obesity and diabetes, of which the characteristic phenotype is gut microbial dysbiosis and impaired intestinal barrier. When the intestinal barrier is damaged, dysbiotic microbiota and their metabolites, as well as dysregulated immune cells, may participate in the reshaping of the local immune microenvironment, and play pivotal roles in the tumorigenesis and development of multiple myeloma, probably by migrating to the bone marrow microenvironment from intestine. We also discuss the emerging microbiological manipulation strategies to improve long-term outcomes of MM, as well as the prospective of the state-of-the-art techniques to advance our knowledge about the biological implication in the microbiome in MM.

miR-576-5p Facilitates Aggressive Cell Behaviors in Colon Adenocarcinoma via Targeting NEGR1.

The microRNA (miRNA) miR-576-5p was reported to facilitate tumor progression, but its underlying regulatory impacts on colon adenocarcinoma remain unknown. This work therefore attempted to examine the biological effects of miR-576-5p in colon adenocarcinoma. The Cancer Genome Atlas (TCGA) database was introduced to analyze miR-576-5p and NEGR1 messenger RNA (mRNA) expression levels between normal and cancer tissues. miR-576-5p and NEGR1 expression levels in colon adenocarcinoma cells and colon cells were evaluated with quantitative reverse transcription polymerase chain reaction (qRT-PCR). NEGR1 protein expression was examined by Western blot. Furthermore, colon adenocarcinoma cell behaviors were evaluated via CCK-8, wound-healing, Transwell, and hanging drop experiments. The interaction between miR-576-5p and NEGRI was verified by dual-luciferase assay. miR-576-5p was upregulated in colon adenocarcinoma, and miR-576-5p overexpression notably facilitated the proliferative, migratory, invasive abilities of colon adenocarcinoma cells. NEGR1 was newly identified as one target of miR-576-5p, and, miR-576-5p/NEGR1 axis was subsequently verified to modulate cell proliferative, migratory, invasive, and aggregate abilities. miR-576-5p facilitated aggressive progression of colon adenocarcinoma cells by targeting NEGR1, which could be an underlying therapeutic target for colon adenocarcinoma.

Proteomics of post-translational modifications in colorectal cancer: Discovery of new biomarkers.

Colorectal cancer (CRC) is one of the costliest health problems and ranks second in cancer-related mortality in developed countries. With the aid of proteomics, many protein biomarkers for the diagnosis, prognosis, and precise management of CRC have been identified. Furthermore, some protein biomarkers exhibit structural diversity after modifications. Post-translational modifications (PTMs), most of which are catalyzed by a variety of enzymes, extensively increase protein diversity and are involved in many complex and dynamic cellular processes through the regulation of protein function. Accumulating evidence suggests that abnormal PTM events are associated with a variety of human diseases, such as CRC, thus highlighting the need for studying PTMs to discover both the molecular mechanisms and therapeutic targets of CRC. In this review, we begin with a brief overview of the importance of protein PTMs, discuss the general strategies for proteomic profiling of several key PTMs (including phosphorylation, acetylation, glycosylation, ubiquitination, methylation, and citrullination), shift the emphasis to describing the specific methods used for delineating the global landscapes of each of these PTMs, and summarize the recent applications of these methods to explore the potential roles of the PTMs in CRC. Finally, we discuss the current status of PTM research on CRC and provide future perspectives on how PTM regulation can play an essential role in translational medicine for early diagnosis, prognosis stratification, and therapeutic intervention in CRC.

[Relationship between the Expression of miRNA181a-5p and the Imbalance of Treg/Th17 in Primary Immune Thrombocytopenia].

OBJECTIVE: To investigate the role of relationship between the expression of miRNA181a-5p and imbalance of Treg/Th17 in the pathogenesis of primary immune thrombocytopenia(ITP), which contributes to clarify the mechanism of T cell immune imbalance in ITP patients. METHODS: Peripheral blood was collected from 37 ITP patients, concluding 21 untreated patients and 16 effectively treated patients, and 19 healthy controls; Peripheral blood mononuclear cells (PBMC) were isolated and the expression of miRNA181a-5p and Notch1 was analyzed by RT-PCR. The proportion of Th17 subsets and Treg cells in the peripheral circulation was detected by flow cytometer (FCM). Clinical data of ITP group was collected, including age, platelet count and disease course. RESULTS: The expression of miR-181a-5p was significantly decreased in ITP group than that of healthy control group (P＜0.01). After effective treatment, the expression of miR-181a-5p was significantly higher than that of ITP group (P＜0.05), but still significantly lower than that of healthy control group (P＜0.01); The expression of Notch1 was significantly increased in ITP group and effectively treated group than that of healthy control group (P＜0.01). There was no significant difference in proportion of Treg cells in ITP group, effectively treated group and healthy control group (P＞0.05). The proportion of Th17 subsets in ITP group was significantly increased than that of healthy control group (P＜0.05), while the ratio of Treg/Th17 was significantly decreased (P＜0.05). There was a positive correlation between the expression of miR-181a-5p and ratio of Treg/Th17 in ITP group (r=0.555). CONCLUSION: The expression of miR-181a-5p is significantly decreased in ITP patients, which is closely related to the imbalance of Treg/Th17 cells. After effective treatment, the expression of miR-181a-5p can be significantly corrected, but still failed to reach the level of healthy people. While the expression of Notch1 is significantly increased in ITP patients, and could not reach the level of healthy people after effective treatment.

Dieckol inhibits non-small-cell lung cancer cell proliferation and migration by regulating the PI3K/AKT signaling pathway.

Non-small-cell lung cancer (NSCLC) is one of the most prevalent type of lung cancers with an increased mortality rate in both developed and developing countries worldwide. Dieckol is one such polyphenolic drug extracted from brown algae which has proven antioxidant and anti-inflammatory properties. In the present study, we evaluated the anticancer property of dieckol against NSCLC cell line A549. The LC50 value of dieckol was found to be 25 µg/mL by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the antiapoptotic property of dieckol was analyzed by dual staining technique with acridine orange/propidium iodide (AO/PI) stains. It was further confirmed with flow cytometry analysis with Annexin FITC and JC-1 staining and the anti-invasive property was assessed by Transwell assay. The molecular mechanism of dieckol anticancer activity was confirmed by estimating the levels of caspases and by estimating the signaling proteins of Pi3K/AKT/mTOR signaling pathway using the immunoblotting technique. Our data suggest that dieckol is potent anticancer agent, it effectively inhibits the invasive and migratory property A549 cells and it also induces apoptosis via inhibiting Pi3K/AKT/mTOR signaling, activating the tumor suppressor protein E-cadherin signifying that dieckol is potent natural anticancer drug to treat NSCLC.