The role of LncRNA-mediated autophagy in cancer progression.

Long non-coding RNAs (lncRNAs) are a sort of transcripts that are more than 200 nucleotides in length. In recent years, many studies have revealed the modulatory role of lncRNAs in cancer. Typically, lncRNAs are linked to a variety of essential events, such as apoptosis, cellular proliferation, and the invasion of malignant cells. Simultaneously, autophagy, an essential intracellular degradation mechanism in eukaryotic cells, is activated to respond to multiple stressful circumstances, for example, nutrient scarcity, accumulation of abnormal proteins, and organelle damage. Autophagy plays both suppressive and promoting roles in cancer. Increasingly, studies have unveiled how dysregulated lncRNAs expression can disrupt autophagic balance, thereby contributing to cancer progression. Consequently, exploring the interplay between lncRNAs and autophagy holds promising implications for clinical research. In this manuscript, we methodically compiled the advances in the molecular mechanisms of lncRNAs and autophagy and briefly summarized the implications of the lncRNA-mediated autophagy axis.

Analysis of complement system and its related factors in Alzheimer's disease.

Alzheimer's disease (AD) is a primary cause of dementia. The complement system is closely related to AD pathology and may be a potential target for the prevention and treatment of AD. In our study, we conducted a bioinformatics analysis to analyze the role of the complement system and its related factors in AD using Gene Expression Omnibus (GEO) data. We also conducted a functional analysis. Our study verified that 23 genes were closely related to differentially expressed complement system genes in diseases after intersecting the disease-related complement system module genes and differentially expressed genes. The STRING database was used to predict the interactions between the modular gene proteins of the differential complement system. A total of 21 gene proteins and 44 interaction pairs showed close interactions. We screened key genes and created a diagnostic model. The predictive effect of the model was constructed using GSE5281 and our study indicated that the predictive effect of the model was good. Our study also showed enriched negative regulation of Notch signaling, cytokine secretion involved in the immune response pathway, and cytokine secretion involved in immune response hormone-mediated apoptotic signaling pathway. We hope that our study provides a promising target to prevent and delay the onset, diagnosis, and treatment of AD.

MicroRNA-153-3p enhances the sensitivity of chronic myeloid leukemia cells to imatinib by inhibiting B-cell lymphoma-2-mediated autophagy.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease caused by abnormal DNA replication of bone marrow stem cells and chemotherapy resistance is a major obstacle to the effective treatment of patients with CML. Imatinib (IM), a tyrosine kinase inhibitor (TKI), is a first-line drug clinically used for CML. Mounting evidence has indicated that the dysregulation of microRNAs (miRNAs) is associated with the chemoresistance of CML. In this study, miR-153-3p, which had been implicated with numerous types of tumors, was identified to be downregulated in IM-resistant CML cells. Upregulation of miR-153-3p significantly increased IM sensitivity and decreased the survival rate of IM-resistant CML cells, whereas downregulation of miR-153-3p attenuated these effects in IM-resistant CML cells. Upregulated miR-153-3p could decrease the autophagy caused by IM in IM-resistant CML cells. Dual-luciferase reporter assays confirmed that Bcl-2 is a direct target of miR-153-3p. Bcl-2 restoration reversed the increased sensitivity to IM induced by miR-153-3p-mimic transfection in IM-resistant CML cells. The results of the present study showed that dysregulated miR-153-3p may target Bcl-2 to promote the development of IM resistance and attenuate IM-induced apoptosis in CML. Therefore, miR-153-3p upregulation combined with IM treatment may serve as a promising therapeutic strategy for patients with low sensitivity.

Synergistic antitumoral activity and induction of apoptosis by novel pan Bcl-2 proteins inhibitor apogossypolone with adriamycin in human hepatocellular carcinoma.

AIM: To investigate the in vitro and in vivo activities and related mechanism of apogossypolone (ApoG2) alone or in combination with adriamycin (ADM) against human hepatocellular carcinoma (HCC). METHODS: The IC50 of ApoG2 in vitro was tested by WST assay, and the synergistic effect was analyzed using the CalcuSyn method. Cell apoptosis was determined using 4',6-diamidino-2- phenylindole staining and flow cytometric analysis. Western blotting was used to determine the expression of apoptosis-related proteins. In vivo activity was evaluated in the xenograft model in nude mice, and apoptosis in tumor tissues was determined by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) assay. RESULTS: The IC50 of ApoG2 in HCC cells was 17.28-30.63 micromol/L. When ApoG2 was combined with ADM, increased cytotoxicity and apoptosis were observed in SMMC-7721 cells compared to treatment with ApoG2 alone. The Western blotting results indicated that the ApoG2 induced apoptosis in SMMC-7721 cells by downregulating anti-apoptotic proteins Bcl-2, Mcl-1, and Bcl-XL, up-regulating pro-apoptotic protein Noxa, and promoting the activities of caspases-9 and -3. The tumor growth of xenograft SMMC-7721 was inhibited in nude mice when ApoG2 was administered orally without causing damage to the normal tissues. The in vivo study also indicated an increasing anti-tumoral effect when ApoG2 at 100 or 200 mg/kg dosages were used together with ADM at 5.5 mg/kg, with relative tumor proliferation rate (T/C) values of 0.456 and 0.323, respectively. Apoptosis induced in vivo by ApoG2 alone or combined with ADM was confirmed by TUNEL assay in tumor tissues. CONCLUSION: ApoG2 is a potential non-toxic target agent that induces apoptosis by upregulating Noxa, while inhibiting anti-apoptotic proteins and promoting the effect of chemotherapy agent ADM in HCC.

[Proteomics analysis of bone marrow cells of acute myeloid leukemia M2a and prognostic significance thereof].

OBJECTIVE: To investigate the relationship between the distinct expression of proteins in the leukemic cells of leukemia AML-M(2)a patients before inducible treatment and that of the patients with relapse and the prognosis by proteomics. METHODS: The bone marrow mononuclear cells (BMMNC) from 17 patients with leukemia AML-M(2)a before inductive treatment were divided into 3 groups according to the duration of CCR(1): Group A (n = 11) with the CCR(1) duration exceeding 12 months, Group B (n = 6) with the CCR(1) duration less than 6 months, and Group C, including the 3 cases of Group B with relapse. The proteins of the BMMNC were separated by two-dimensional electrophoresis, part of the differentially-expressed proteins were identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: 6 differentially-expressed proteins were identified between Groups A and B by MALDI-TOF-MS: tubulin-specific chaperone B, myeloperoxidase, the CH domain of human transgelin-2, glutathione S-transferase, zinc finger protein, and glyceraldehyde-3-phosphate dehydrogenase. Three differentially-expressed proteins were identified in Group C: NAD (P) H dehydrogenase, hypothetical protein, and HES1. CONCLUSION: The expression level of distinct proteins of leukemic cells of leukemia AML-M(2)a patients before inductive treatments is associated with the prognosis. The proteins of the BMMNC of the patients would change when relapse occurs.

[Gene expression profile of refractory acute myeloid leukemia (M2a)].

BACKGROUND & OBJECTIVE: Recurrence is the major cause of treatment failure of acute myeloid leukemia (AML). At recurrence, some patients show changes in immunophenotype and cytogenetics. Drug resistance, the main cause of refractoriness of AML, is related to abnormal genes expression. This study was to detect differential expression of genes in naive and recurrent/refractory AML, and explore potential mechanisms of recurrent/refractory AML. METHODS: Differential gene expressions of bone marrow mononuclear cells between naive and recurrent/refractory diseases in 5 self-paired patients with AML-M(2a) were detected by DNA microarray. RESULTS: In 925 tested genes, 14 were differentially expressed between naive and recurrent/refractory diseases in the 5 self-paired patients. Of the 14 genes, 12 (involved in signal transduction, DNA replication, regulation of transcription, RNA processing, and regulation of cell cycle) were obviously up-regulated in recurrent diseases, and up-regulation of RRM1 (involved in DNA replication) was the most obvious. CONCLUSIONS: Development of recurrent/refractory AML-M(2a) is concerned with various genes. Up-regulation of these genes suggests that proliferation of recurrent/refractory AML-M(2a) blasts may be higher than that of naive AML-M(2a) blasts.

[Evolution of gene expression profile in 3 cases of acute myeloid leukemia].

OBJECTIVE: To investigate the mechanism of refractoriness of acute myeloid leukemia (AML) by studying the changes of gene mRNA expression from primary diagnosis to relapsed disease in AML. METHODS: Differences in gene expression profile of bone marrow mononuclear cells were compared between primary diagnosis and relapsed/refractory disease in 3 patients with M(2a) subtype of AML using Agilent human 1B 60mer oligonucleotide microarray. RESULTS: Common alterations were found in 10 genes among the 20173 genes tested at relapsed/refractory disease as compared with that at primary diagnosis in 3 patients. Of these 10 genes, 7 were up-regulated while 3 down-regulated at relapse in all the 3 patients. CONCLUSION: Development of relapsed/refractory disease in AML-M(2a) might be associated with the mRNA expression changes in the 10 genes tested including DAPK1. The alteration of these genes may be indications for the early diagnosis of refractoriness of AML, and these genes might provide new therapeutic targets for the treatment of refractory AML.

[Comparison of vitrification cryopreservation among different stages of mouse embryos].

The cryopreservation of different embryo stages collected from ICR, C57BL/6 and F1 of DBA*C57BL/6 was carried out by using vitrification method. The morphology, in vitro development and birth rates of these embryos were compared after frozen-thawed. The results showed that more than 75% of the morphology from 2-cell embryos to morula stages from different strains was normal, the normal morphology rates of 8-cell embryos being the highest, while those of blastulas being the lowest. The in vitro development rates became higher as the embryos developed. The morphology of in vivo and in vitro fertilized frozen 2-cell embryos showed no difference, but the development rate of in vivo fertilized frozen 2-cell embryos was significantly higher than that of in vitro ones. Embryos that underwent 3 times frozen-thawing remained normal morphology. The pregnant rate and birth rate of frozen 2-cell embryos after embryo transfer were 64% and 40% respectively, but lower than those of fresh 2-cell embryo transfer.