In silico analysis of the wild-type and mutant-type of BRCA2 gene.

BACKGROUND: The aim of this study was to conduct an in silico analysis of a novel compound heterozygous variant in breast cancer susceptibility gene 2 (BRCA2) to clarify its structure-function relationship and elucidate the molecular mechanisms underlying triple-negative breast cancer (TNBC). METHODS: A tumor biopsy sample was obtained from a 42-year-old Chinese woman during surgery, and a maxBRCA™ test was conducted using the patient's whole blood. We obtained an experimentally determined 3D structure (1mje.pdb) of the BRCA2 protein from the Protein Data Bank (PDB) as a relatively reliable reference. Subsequently, the wild-type and mutant structures were predicted using SWISS-MODEL and AlphaFold, and the accuracy of these predictions was assessed through the SAVES online server. Furthermore, we utilized a high ambiguity-driven protein-protein docking (HADDOCK) algorithm and protein-ligand interaction profiler (PLIP) to predict the pathogenicity of the mutations and elucidate pathogenic mechanisms that potentially underlies TNBC. RESULTS: Histological examination revealed that the tumor biopsy sample exhibited classical pathological characteristics of TNBC. Furthermore, the maxBRCA™ test revealed two compound heterozygous BRCA2 gene mutations (c.7670 C > T.pA2557V and c.8356G > A.pA2786T). Through performing in silico structural analyses and constructing of 3D models of the mutants, we established that the mutant amino acids valine and threonine were located in the helical domain and oligonucleotide binding 1 (OB1), regions that interact with DSS1. CONCLUSION: Our analysis revealed that substituting valine and threonine in the helical domain region alters the structure and function of BRCA2 proteins. This mutation potentially affects the binding of proteins and DNA fragments and disrupts interactions between the helical domain region and OB1 with DSS1, potentially leading to the development of TNBC. Our findings suggest that the identified compound heterozygous mutation contributes to the clinical presentation of TNBC, providing new insights into the pathogenesis of TNBC and the influence of compound heterozygous mutations in BRCA2.

Colorectal cancer's burden attributable to a diet high in processed meat in the Belt and Road Initiative countries.

BACKGROUND: Colorectal cancer (CRC) plays a significant role in morbidity, mortality, and economic cost in the Belt and Road Initiative ("B and R") countries. In addition, these countries have a substantial consumption of processed meat. However, the burden and trend of CRC in relation to the consumption of a diet high in processed meat (DHPM-CRC) in these "B and R" countries remain unknown. AIM: To analyze the burden and trend of DHPM-CRC in the "B and R" countries from 1990 to 2019. METHODS: We used the 2019 Global Burden of Disease Study to collate information regarding the burden of DHPM-CRC. Numbers and age-standardized rates (ASRs) of deaths along with the disability-adjusted life years (DALYs) were determined among the "B and R" countries in 1990 and 2019. Using joinpoint regression analysis, the average annual percent change (AAPC) was used to analyze the temporal trends of age-standardized DALYs rate (ASDALR) from 1990 to 2019 and in the final decade (2010-2019). RESULTS: We found geographical differences in the burden of DHPM-CRC among "B and R" countries, with the three highest-ranking countries being the Russian Federation, China, and Ukraine in 1990, and China, the Russian Federation, and Poland in 2019. The burden of DHPM-CRC generally increased in most member countries from 1990 to 2019 (all P < 0.05). The absolute number of deaths and DALYs in DHPM-CRC were 3151.15 [95% uncertainty interval (UI) 665.74-5696.64] and 83249.31 (95%UI 15628.64-151956.31) in China in 2019. However, the number of deaths (2627.57-2528.51) and DALYs (65867.39-55378.65) for DHPM-CRC in the Russian Federation has declined. The fastest increase in ASDALR for DHPM-CRC was observed in Vietnam, Southeast Asia, with an AAPC value of 3.90% [95% confidence interval (CI): 3.63%-4.16%], whereas the fastest decline was observed in Kyrgyzstan, Central Asia, with an AAPC value of -2.05% (95% CI: -2.37% to -1.73%). A substantial upward trend in ASR of mortality, years lived with disability, years of life lost, and DALYs from DHPM-CRC changes in 1990-2019 and the final decade (2010-2019) for most Maritime Silk Route members in East Asia, South Asia, Southeast Asia, North Africa, and the Middle East, as well as Central Europe, while those of the most Land Silk Route members in Central Asia and Eastern Europe have decreased markedly (all P < 0.05). The ASDALR for DHPM-CRC increased more in males than in females (all P < 0.05). For those aged 50-74 years, the ASDALR for DHPM-CRC in 40 members exhibited an increasing trend, except for 20 members, including 7 members in Central Asia, Maldives, and 12 high or high-middle social development index (SDI) members in other regions (all P < 0.05). CONCLUSION: The burden of DHPM-CRC varies substantially across "B and R" countries and threatens public health. Relevant evidence-based policies and interventions tailored to the different trends of countries in SDIs or Silk Routes should be adopted to reduce the future burden of CRC in "B and R" countries via extensive collaboration.

Bioinformatics combined with clinical data to analyze clinical characteristics and prognosis in patients with HER2 low expression breast cancer.

Background: Human epidermal growth factor receptor 2 (HER2) is a landmark protein in determining the targeted treatment of breast cancer (BC). However, the latest research shows that different intensity of HER2 protein expression levels in BC leads to different clinical characteristics, treatment, and prognosis, especially in HER2 low expression patients. Therefore, this study intends to analyze and compare the clinicopathologic features and prognosis of BC patients with low and zero HER2 expression from The Cancer Genome Atlas (TCGA) database and the data collected by our center. Methods: First, the BC dataset was downloaded from TCGA database, including 345 eligible and with complete clinical information BC patients, to compare the difference between HER2 low expression groups and HER2 zero expression groups and their correlation with estrogen receptor (ER) and progesterone receptor (PR) expression. Then, the clinicopathological data and follow-up of 405 patients with HER2 low expression and HER2 zero expression diagnosed with BC admitted to the Affiliated Hospital of Youjiang Medical University for Nationalities (YJMU) from January 2017 to December 2021 were collected to verify the consistency of the results of the two data sets. Results: Both the clinical samples and the TCGA data showed that the ER and PR rates were higher in the HER2 low expression group compared with the HER2 zero expression group. There were no significant differences in tumor size, lymph node metastasis, distant metastasis, and disease-free survival (DFS). In addition, the data analysis of 405 clinical samples also showed that the HER2 low expression group had a lower 3-year recurrence or metastasis rate compared with the HER2 zero expression group. Conclusions: Compared with HER2 zero expression, HER2 low patients express more ER and PR, and have less short-term recurrence and metastasis, but there is no obvious difference in DFS between the two groups.

Advanced Platelet-Rich Fibrin Extract Treatment Promotes the Proliferation and Differentiation of Human Adipose-Derived Mesenchymal Stem Cells through Activation of Tryptophan Metabolism.

BACKGROUND: Advanced platelet-rich fibrin extract (APRFE) contains a high concentration of various cytokines that are helpful for improving stem cells repair function. OBJECTIVE: However, the underlying mechanism of APRFE improving stem cell repairing is not clear. METHODS: We produced APRFE by centrifuging fresh peripheral blood samples and isolated and identified human adipose-derived mesenchymal stem cells (ADMSCs). The abundance of cytokines contained in APRFE was detected by the Enzyme-linked immunosorbent assay (ELISA). The ADMSCs treated with or without APRFE were collected for transcriptome sequencing. RESULTS: Based on the sequencing data, the expression profiles were contracted. The differentially expressed genes and lncRNA (DEGs and DElncRNAs) were obtained using for the differential expression analysis. The lncRNA-miRNA-mRNA network was constructed based on the miRNet database. The further enrichment analysis results showed that the biological functions were mainly related to proliferation, differentiation, and cell-cell function. To explore the role of APRFE, the protein-protein interaction network was constructed among the cytokines included in APRFE and DEGs. Furthermore, we constructed the global regulatory network based on the RNAInter and TRRUST database. The pathways in the global regulatory network were considered as the core pathways. We found that the DEGs in the core pathways were associated with stemness scores. CONCLUSION: In summary, we predicted that APRFE activated three pathways (tryptophan metabolism, mTOR signaling pathway, and adipocytokine signaling) to promote the proliferation and differentiation of ADMSCs. The finding may be helpful for guiding the application of ADMSCs in the clinic.

Endothelial Cells Potentially Participate in the Metastasis of Triple-Negative Breast Cancer.

Inhibition of triple-negative breast cancer metastasis has long been a challenge, mainly due to the difficulty in identifying factors that contribute to this process. In this study, freshly isolated triple-negative breast cancer biopsied cells obtained from consenting patients were subjected to flow cytometry and bioinformatic analysis to identify three endothelial cell subclusters: EC (ATP1B3), EC (HSPA1B), and EC (KRT7) in the tumor microenvironment. These endothelial cell subclusters exhibited distinguishing biological features. Based on differentially expressed genes derived from the subclusters, gene set enrichment analysis showed that EC (ATP1B3) and EC (HSPA1B) contribute to the process of metastasis, for example, in fibrosarcoma and anaplastic carcinoma. In this study, we identified the heterogeneity of endothelial cells in the human breast cancer and have provided insights into its role in metastasis.

3D-Printed Degradable Anti-Tumor Scaffolds for Controllable Drug Delivery.

In this study, porous polylactic acid/methotrexate (PLA/MTX) scaffolds were successfully fabricated by three-dimensional (3D) printing technology as controllable drug delivery devices to suppress tumor growth. Scanning electron microscopy and energy-dispersive spectrometer confirmed that MTX drug was successfully incorporated into the PLA filament. 3D-printed PLA/MTX scaffolds allow sustained release of drug molecules in vitro for more than 30 days, reducing systemic toxic side effects caused by injection or oral administration. In vitro cytotoxicity assay revealed that PLA/MTX scaffolds have a relatively high inhibitory effect on the tumor cells (MG-63, A549, MCF-7, and 4T1) and relatively low toxic effect on the normal MC3T3-E1 cells. Furthermore, results of in vivo experiments confirmed that PLA/MTX scaffolds highly suppressed tumor growth and no obvious side effects on the organs. All these results suggested that 3D-printed PLA/MTX scaffolds could be used as controllable drug delivery systems for tumor suppression.

Single-Cell Analyses Reveal Mechanisms of Cancer Stem Cell Maintenance and Epithelial-Mesenchymal Transition in Recurrent Bladder Cancer.

PURPOSE: Bladder cancer treatment remains a major clinical challenge due to therapy resistance and a high recurrence rate. Profiling intratumor heterogeneity can reveal the molecular mechanism of bladder cancer recurrence. EXPERIMENTAL DESIGN: Here, we performed single-cell RNA sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) on tumors from 13 patients with low recurrence risk, high recurrence risk, and recurrent bladder cancer. RESULTS: Our study generated a comprehensive cancer-cell atlas consisting of 54,971 single cells and identified distinct cell subpopulations. We found that the cancer stem-cell subpopulation is enriched during bladder cancer recurrence with elevated expression of EZH2. We further defined a subpopulation-specific molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression of the NCAM1 gene, thereby inactivating the cell invasive and stemness transcriptional program. Furthermore, taking advantage of this large single-cell dataset, we elucidated the spectrum of epithelial-mesenchymal transition (EMT) in clinical samples and revealed distinct EMT features associated with bladder cancer subtypes. We identified that TCF7 promotes EMT in corroboration with single-cell ATAC with high-throughput sequencing (scATAC-seq) analysis. Additionally, we constructed regulatory networks specific to recurrent bladder cancer. CONCLUSIONS: Our study and analytic approaches herein provide a rich resource for the further study of cancer stem cells and EMT in the bladder cancer research field.

Single-cell analyses reveal suppressive tumor microenvironment of human colorectal cancer.

Profiling heterologous cell types within tumors is essential to decipher tumor microenvironment that shapes tumor progress and determines the outcome of therapeutic response. Here, we comprehensively characterized transcriptomes of 34,037 single cells obtained from 12 treatment-naïve patients with colorectal cancer. Our comprehensive evaluation revealed attenuated B-cell antigen presentation, distinct regulatory T-cell clusters with different origin and novel polyfunctional tumor associated macrophages associated with CRC. Moreover, we identified expanded XCL1+ T-cell clusters associated with tumor mutational burden high status. We further explored the underlying molecular mechanisms by profiling epigenetic landscape and inferring transcription factor motifs using single-cell ATAC-seq. Our dataset and analysis approaches herein provide a rich resource for further study of the impact of immune cells and translational research for human colorectal cancer.

The immune-related gene CD52 is a favorable biomarker for breast cancer prognosis.

BACKGROUND: An increasing number of studies have demonstrated a role for the tumor microenvironment in tumorigenesis, disease progression, and therapeutic response. This present study aimed to screen the significant immune-related genes and their possible role in the prognosis of breast cancer (BRCA). METHODS: The transcriptome data and clinical data of breast cancer were collected from The Cancer Genome Atlas (TCGA), and the immune scores and stromal scores were calculated by ESTIMATE algorithm. The differentially expressed genes were screened base on immune and stromal scores (high score vs. low score), than the intersected genes were used for subsequent functional enrichment analysis and protein-protein interaction (PPI) analysis. Furthermore, the key gene was identified by the intersection of the hub genes of PPI network and the prognostic genes of breast cancer. Finally, we explored the infiltration of immune cells of BRCA base on the CIBERSORT algorithm, and analysis the relationship between key gene and immune cells. RESULTS: High levels of CD52 expression were detected in the early stages of breast cancer and were associated with favorable prognosis. Overexpression of CD52 led to higher infiltrations of M1 macrophages, monocytes, T follicular helper cells, and resting memory CD4 T cells. Downregulation of CD52 resulted in high infiltrations of M2 macrophages. Therefore, high expression of CD52 may negatively regulate the infiltration of M2 macrophages but accelerate the infiltration of anti-cancer immune cells, and thus, high expression of CD52 may have a protective effect in breast cancer patients. CONCLUSIONS: CD52 can increase the infiltration of anti-cancer immune cells but inhibit the infiltration of M2 macrophages, thereby improving the prognosis of breast cancer patients.

Postponing tumor onset and tumor progression can be achieved by alteration of local tumor immunity.

BACKGROUND: It has been known for years that the same genetic defects drive breast cancer formation, yet, the onset of breast cancer in different individuals among the same population differs greatly in their life spans with unknown mechanisms. METHODS: We used a MMTV-PyMT mouse model with different genetic backgrounds (FVB/NJ vs. C57BL/6J) to generate different cancer onset phenotypes, then profiled and analyzed the gene expression of three tumor stages in both Fvb.B6 and Fvb mice to explore the underlying mechanisms. RESULTS: We found that in contrast with the FVB/N-Tg (MMTV-PyMT) 634Mul mice (Fvb mice), mammary tumor initiation was significantly delayed and tumor progression was significantly suppressed in the Fvb.B6 mice (generated by crossing FVB/NJ with C57BL/6J mice). Transcriptome sequencing and analysis revealed that the differentially expressed genes were enriched in immune-related pathways. Flow cytometry analysis showed a higher proportion of matured dendritic cells in the Fvb.B6 mice. The plasma levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were significantly reduced in the Fvb.B6 mice. IL-6 also impaired the maturation of bone marrow dendritic cells (BMDCs) of the Fvb mice in vitro. CONCLUSION: All these findings suggest that immunity levels (characterized by a reduced IL-6 level and intact DC maturation in Fvb.B6 mice) are the key factors affecting tumor onset in a murine mammary cancer model.

Deeply Recursive Low- and High-Frequency Fusing Networks for Single Image Super-Resolution.

With the development of researches on single image super-resolution (SISR) based on convolutional neural networks (CNN), the quality of recovered images has been remarkably promoted. Since then, many deep learning-based models have been proposed, which have outperformed the traditional SISR algorithms. According to the results of extensive experiments, the feature representations of the model can be enhanced by increasing the depth and width of the network, which can ultimately improve the image reconstruction quality. However, a larger network generally consumes more computational and memory resources, making it difficult to train the network and increasing the prediction time. In view of the above problems, a novel deeply-recursive low- and high-frequency fusing network (DRFFN) for SISR tasks is proposed in this paper, which adopts the structure of parallel branches to extract the low- and high-frequency information of the image, respectively. The different complexities of the branches can reflect the frequency characteristic of the diverse image information. Moreover, an effective channel-wise attention mechanism based on variance (VCA) is designed to make the information distribution of each feature map more reasonably with different variances. Owing to model structure (i.e., cascading recursive learning of recursive units), DRFFN and DRFFN-L are very compact, where the weights are shared by all convolutional recursions. Comprehensive benchmark evaluations in standard benchmark datasets well demonstrate that DRFFN outperforms the most existing models and has achieved competitive, quantitative, and visual results.

Expression and role of nuclear receptor-interacting protein 1 (NRIP1) in stomach adenocarcinoma.

BACKGROUND: Nuclear receptor-interacting protein 1 (NRIP1), also named NR140, has been observed differentially express in multiple cancers, but the expression levels and the prognostic role of NRIP1 in stomach adenocarcinoma (STAD) remain unclear. METHODS: We used the Gene Expression Profiling Interactive Analysis (GEPIA) to analyze the NRIP1 expression levels in STAD, subgroups analysis of expression of NRIP1 via the UALCAN dataset. Further, cBioPortal was used to investigate the aberration type, co-mutations status, and located mutation of NRIP1. Correlated genes, and kinases, microRNA (miRNA), and transcription factor (TF) targets were identified using LinkedOmics. The Kaplan-Meier (K-M) plotter was used to analyze the prognosis of NRIP1 and the significantly correlated genes in STAD. Then, the tumor immune estimation resource (Timer) was used to explore the relation between NRIP1 and the immune cell infiltration, and the role of immune cells in STAD. The Human Protein Atlas (HPA) was used to confirm the NRIP1 protein express in STAD stomach tissue and normal stomach tissue. RESULTS: NRIP1 significantly overexpress in STAD, and the NRIP1 expression levels were impacted by clinical features. Overexpression of NRIP1 indicated the poor prognosis of STAD. Functional enrichment analysis showed the NRIP1 mainly enriched in immune response-regulating signaling pathway, cell-substrate adhesion, mRNA processing, and pathway in cancer. Overexpression USP25, SNYJ1 indicated the poor outcome of STAD, but the overexpression of BACH1 indicated protective biomarker. MIR-331 and MIR-132 have important role in STAD. Further, NRIP1 had a significant relation with immune infiltrates and other defined genes that significantly impact immune infiltrates. Immunohistochemical showed NRIP1 protein was higher in STAD than normal sample. CONCLUSIONS: In this study, we revealed that overexpression of NRIP1 in the STAD sample compared to normal samples, NRIP1 significantly associated with macrophage. The high expression levels of NRIP1 and more macrophage infiltration led to poor prognosis of STAD.

Landscape of transcription and expression regulated by DNA methylation related to age of donor and cell passage in adipose-derived mesenchymal stem cells.

Adipose-derived mesenchymal stem cells (ADSCs) are pluripotent stromal cells that can differentiate into a variety of cell types, including skin cells. High-throughput sequencing was performed on cells of different ages and cell passage, obtaining their methylation, mRNA expression, and protein profile data. The stemness of each sample was then calculated using the TCGAbiolinks package in R. Co-expression modules were identified using WGCNA, and a crosstalk analysis was performed on the corresponding modules. The ClusterProfile package was used for the functional annotation of module genes. Finally, the regulatory network diagram was visualized using the Cytoscape software. First, a total of 16 modules were identified, where 3 modules were screened that were most relevant to the phenotype. 29 genes were screened in combination of the RNA seq, DNA methylation seq and protein iTRAQ. Finally, a comprehensive landscape comprised of RNA expression, DNA methylation and protein profiles of age relevant ADSCs was constructed. Overall, the different omics of ADSCs were comprehensively analyzed in order to reveal mechanisms pertaining to their growth and development. The effects of age, cell passage, and stemness on the therapeutic effect of ADSCs were explored. Additionally, a theoretical basis for selecting appropriate ADSC donors for regenerative medicine was provided.

Long Non-coding RNA RP11-480I12.5 Promotes the Proliferation, Migration, and Invasion of Breast Cancer Cells Through the miR-490-3p-AURKA-Wnt/ß-Catenin Axis.

Background: RP11-480I12. 5 is a newly identified long non-coding RNA (lncRNA) that has never been studied in breast cancer (BC). The biological function of RP11-480I12.5 in breast carcinoma and its underlying mechanism are still unknown. Methods: We scanned The Cancer Genome Atlas (TCGA) database and identified RP11-480I12.5 as one of the most dysregulated lncRNAs. The level of RP11-480I12.5 was assessed in BC tissue samples and BC cell lines. The prognostic value of RP11-480I12.5 expression was assessed using the Kaplan-Meier method. The biological influence of RP11-480I12.5 on BC cell lines was studied using proliferation and Transwell migration and invasion assays. Results: RP11-480I12.5 expression was upregulated in data from both the TCGA database and our own database. Moreover, Kaplan-Meier and Cox proportional hazard analyses indicated that high RP11-480I12.5 expression was related to poor overall survival. Moreover, RP11-480I12.5 promoted the proliferation, migration, and invasion of BC. RP11-480I12.5 promoted the expression of AURKA and the activation of the downstream Wnt/ß-catenin pathway by sponging the microRNA (miRNA) miR-490-3p. Conclusion: Taken together, our results indicate that RP11-480I12.5 is associated with tumor progression in BCs. Our findings indicate that the lncRNA RP11-480I12.5 promotes the proliferation, migration, and invasion of BC cells through the miR-490-3p-AURKA-Wnt/ß-catenin axis, which may serve as a therapeutic target in the future.

Multiomics global landscape of stemness-related gene clusters in adipose-derived mesenchymal stem cells.

BACKGROUND: Adipose-derived mesenchymal stem cells (AD-MSCs) are a type of stem cell that is abundant and widely used. The molecular characteristics of AD-MSCs from different passages from donors of different ages have not been well elucidated. METHODS: Six kinds of AD-MSCs ((E1, E2, E3, Y1, Y2, and Y3) with E denoting cells derived from an elderly patient, Y denoting cells derived from a young patient, and 1, 2, and 3 representing passages 3, 6, and 10) were obtained from human abdominal adipose tissue. We obtained the protein expression profile, the mRNA expression profile, the lncRNA expression profile, and the methylation profile of each kind of AD-MSC by sequencing. After calculating the stemness indices, genes related to stemness were extracted. The multiomics correlation analysis was performed in the stemness-related genes. In addition, short time-series expression miner (STEM) analysis was performed for all cell passages and donor ages. To further explore the biological functions of the stemness-related genes, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, the lncRNA-KEGG network and transcription factor (TF)-KEGG network were constructed based on the RNAInter database and TRRUST v2 database. RESULTS: The stemness of the Y1, E1, and Y2 cells was higher than that of the E2, Y3, and E3 cells. The stemness was the highest for Y1 cells and the lowest for E3 cells. STEM analysis showed that five stemness-related gene clusters were associated with the cell passages, and only one gene cluster was associated with age. The enrichment analysis results showed that the biological processes (BPs) and KEGG pathways were mainly involved in the proliferation, differentiation, and migration of cells. The global regulatory landscape of AD-MSCs was constructed: 25 TFs and 16 lncRNAs regulated 21 KEGG pathways through 27 mRNAs. Furthermore, we obtained a core stemness-related gene set consisting of ITGAV, MAD2L1, and PCNA. These genes were expressed at higher levels in Y1 cells than in E3 cells. CONCLUSION: The multiomics global landscape of stemness-related gene clusters was determined for AD-MSCs, which may be helpful for selecting AD-MSCs with increased stemness.

FGF2-induced PI3K/Akt signaling evokes greater proliferation and adipogenic differentiation of human adipose stem cells from breast than from abdomen or thigh.

In this study, human adipose stem cells were isolated from subcutaneous fat in the thigh (htASCs), abdomen (haASCs) and breast (hbASCs). Flow cytometry was used to detect cell surface markers, and an enzyme-linked immunosorbent assay was used to detect paracrine activity. Paracrine gene expression in the three cell types was examined using real-time qPCR, and adipogenic ability was assessed using Oil Red O staining. RNA from third-passage haASCs and hbASCs was sequenced. The results showed that the differentiation potential marker markers CD49d and CD54 were similar across hbASCs from 10 subjects. The hbASCs showed higher colony forming ability and expression of fibroblast growth factor-2, tissue inhibitor of metalloproteinase-1 and stromal cell derived factor-1 than htASCs and haASCs. Stimulating hbASCs with FGF2 promoted adipogenic differentiation, while treating the cells with the PI3K inhibitor LY294002 inhibited differentiation. These results suggest that the PI3K/Akt signaling pathway can promote proliferation and adipogenic differentiation of adipose stem cells, and that activation of this pathway by FGF2 may explain why hbASCs show greater proliferation and adipogenic differentiation than haASCs and htASCs.

A method to establish a c-Myc transgenic mouse model of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains one of the most lethal malignant cancers worldwide. HCC mouse models are widely used to explore the molecular pathogenesis of HCC and to test novel drug candidates. The advantages of this mouse model are as follows:•This method developed a H11LNL-Myc knock-in HCC mouse model by crossing H11LNL-Myc heterozygous mice with (albumin (Alb))-cre transgenic mice to generate c-Myc/Alb-cre double positive mice.•The c-Myc/Alb-cre double-positive mice exhibited a typical HCC phenotype, and showed accelerated tumor initiation and rapid HCC progression. Early stage HCC tumors (2-3 mm in diameter) were observed in male mice at the age of 47 days and in female mice at the age of 60 days.•Approximately 3 months later, the HCC tumors had progressed to a late stage (> 1 cm in diameter), and 100% of the male and female mice had HCC.

Mitochondrial fission regulator 2 (MTFR2) promotes growth, migration, invasion and tumour progression in breast cancer cells.

INTRODUCTION: Mitochondrial fission regulator 2 (MTFR2) belongs to the MTFR family, and 2 isoforms of MTFR2 are produced by alternative splicing. The role of MTFR2 in breast cancer (BC) remains unknown. RESULTS: MTFR2 was upregulated in BC tissues and was strongly associated with tumor characteristics. Moreover, Kaplan-Meier and Cox proportional hazards analyses indicated that high MTFR2 expression was related to poor overall survival. In addition, the capacity for migration and invasion decreased in two BC cell lines after knockdown of MTFR2. The epithelial-mesenchymal transition pathway was inhibited in MTFR2-silenced cells. MTFR2 can switch glucose metabolism from OXPHS to glycolysis in a HIF1α- and HIF2α-dependent manner. CONCLUSION: Taken together, our results indicate that increased expression of MTFR2 is associated with tumour progression in breast cancer cells through switching glucose metabolism from OXPHS to glycolysis in a HIF1α- and HIF2α-dependent manner. MATERIALS AND METHODS: We obtained data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to analyse MTFR2 expression in BC. The prognostic value of MTFR2 expression was assessed using the Kaplan-Meier method. The biological influence of MTFR2 on BC cell lines was studied using proliferation, Transwell migration, invasion and mitochondrial function assays.

A Case-Control Study of the Association Between the SPP1 Gene SNPs and the Susceptibility to Breast Cancer in Guangxi, China.

Secreted phosphoprotein-1 (SPP1) has been reported to be involved in the pathogenesis of breast cancer (BRC), but the influence of SPP1 single nucleotide polymorphisms on the BRC susceptibility has been rarely reported. In this study, we explored the association between rs11730582, rs2853750, and rs35893069 in the SPP1 gene and the BRC susceptibility. We used Snapshot assay to detect SPP1 single nucleotide polymorphisms in 471 BRC patients and 471 controls. The plasma SPP1 level was measured by ELISA. We found that the CC genotype and C allele of rs11730582 were associated with a significantly decreased BRC risk compared with the TT genotype and T allele, respectively [CC vs. TT: odds ratio (OR) = 0.59, 95% CI = 0.37-0.94, P = 0.026; C vs. T: OR = 0.79, 95% CI = 0.65-0.96, P = 0.022]. In addition, BRC patients and controls with the rs11730582 CC genotype had a lower plasma SPP1 level than did BRC patients and controls with TT genotype (P = 0.007 and P = 0.011, respectively). Moreover, the proportions of rs11730582 CC genotype and C allele were decreased in BRC patients with clinical stages I-III compared with those with clinical stage IV (P = 0.012 and P = 0.003, respectively). Besides, the C-G-T haplotype was associated with a significantly decreased BRC risk compared with the T-A-T haplotype (OR = 0.69, 95% CI = 0.52-0.93, P = 0.015). However, there was no significant association between rs2853750 or rs35893069 and the BRC risk. In summary, our study found the association between rs11730582 and the risk of BRC and suggested that rs11730582 may promote the occurrence and development of BRC by regulating SPP1 expression.