Clustered surface amino acid residues modulate the acid stability of GH10 xylanase in fungi.

Acidic xylanases are widely used in industries such as biofuels, animal feeding, and fruit juice clarification due to their tolerance to acidic environments. However, the factors controlling their acid stability, especially in GH10 xylanases, are only partially understood. In this study, we identified a series of thermostable GH10 xylanases with optimal temperatures ranging from 70 to 90 °C, and among these, five enzymes (Xyn10C, Xyn10RE, Xyn10TC, Xyn10BS, and Xyn10PC) exhibited remarkable stability at pH 2.0. Our statistical analysis highlighted several factors contributing to the acid stability of GH10 xylanases, including electrostatic repulsion, π-π stacking, ionic bonds, hydrogen bonds, and Van der Waals interactions. Furthermore, through mutagenesis studies, we uncovered that acid stability is influenced by a complex interplay of amino acid residues. The key amino acid sites determining the acid stability of GH10 xylanases were thus elucidated, mainly concentrated in two surface regions behind the enzyme active center. Notably, the critical residues associated with acid stability markedly enhanced Xyn10RE's thermostability by more than sixfold, indicating a potential acid-thermal interplay in GH10 xylanases. This study not only reported a series of valuable genes but also provided a range of modification targets for enhancing the acid stability of GH10 xylanases. KEY POINTS: • Five acid stable and thermostable GH10 xylanases were reported. • The key amino acid sites, mainly forming two enriched surface regions behind the enzyme active center, were identified responsible for acid stability of GH10 xylanases. • The finding revealed interactive amino acid sites, offering a pathway for synergistic enhancement of both acid stability and thermostability in GH10 xylanase modifications.

Genome-Wide Identification of LBD Genes in Foxtail Millet (Setaria italica) and Functional Characterization of SiLBD21.

Plant-specific lateral organ boundaries domain (LBD) proteins play important roles in plant growth and development. Foxtail millet (Setaria italica) is one new C4 model crop. However, the functions of foxtail millet LBD genes are unknown. In this study, a genome-wide identification of foxtail millet LBD genes and a systematical analysis were conducted. A total of 33 SiLBD genes were identified. They are unevenly distributed on nine chromosomes. Among these SiLBD genes, six segmental duplication pairs were detected. The thirty-three encoded SiLBD proteins could be classified into two classes and seven clades. Members in the same clade have similar gene structure and motif composition. Forty-seven kinds of cis-elements were found in the putative promoters, and they are related to development/growth, hormone, and abiotic stress response, respectively. Meanwhile, the expression pattern was investigated. Most SiLBD genes are expressed in different tissues, while several genes are mainly expressed in one or two kinds of tissues. In addition, most SiLBD genes respond to different abiotic stresses. Furthermore, the function of SiLBD21, which is mainly expressed in roots, was characterized by ectopic expression in Arabidopsis and rice. Compared to controls, transgenic plants generated shorter primary roots and more lateral roots, indicating the function of SiLBD21 in root development. Overall, our study laid the foundation for further functional elucidation of SiLBD genes.

Elevation of microRNA-365 impedes malignant behaviors of gastric cancer cells by inhibiting PAX6.

MicroRNA-365 (miR-365) has been revealed to be a vital regulator in tumorigenesis of multiple cancers, while there is a large gap in the knowledge about miR-365 expression and gastric cancer (GC). This research focused on the effects of miR-365 and paired box 6 (PAX6) on GC development. Levels of miR-365 and PAX6 in GC tissues and cell lines were determined, followed by the screening of the AGS and NCI-N87 cells. Gain- or loss-of-function assays were used to analyze the effect of miR-365, PAX6 on AGS and NCI-N87 cell behaviors. The effects of altered miR-365 and PAX6 on animal models were observed. Moreover, to assess the interaction between miR-365 and PAX6, we implemented the bioinformatic method and dual luciferase reporter gene assay. MiR-365 was decreased while PAX6 was increased in GC tissues and cell lines. There existed a negative association between miR-365 and PAX6. The promoted miR-365 could repress oncogenicity in vivo and malignant transformation in vitro of GC. PAX6 was the target gene of miR-365. Overexpression of PAX6 reversed the inhibitory effect of up-regulated miR-365 on malignant behavior of gastric cancer cells. Our research displays that the amplification of miR-365 could suppress the malignant behaviors of GC cells via inhibiting PAX6, which may be helpful for GC treatment.

Polysaccharides from Medicine and Food Homology Materials: A Review on Their Extraction, Purification, Structure, and Biological Activities.

Medicine and food homology (MFH) materials are rich in polysaccharides, proteins, fats, vitamins, and other components. Hence, they have good medical and nutritional values. Polysaccharides are identified as one of the pivotal bioactive constituents of MFH materials. Accumulating evidence has revealed that MFH polysaccharides (MFHPs) have a variety of biological activities, such as antioxidant, immunomodulatory, anti-tumor, hepatoprotective, anti-aging, anti-inflammatory, and radioprotective activities. Consequently, the research progress and future prospects of MFHPs must be systematically reviewed to promote their better understanding. This paper reviewed the extraction and purification methods, structure, biological activities, and potential molecular mechanisms of MFHPs. This review may provide some valuable insights for further research regarding MFHPs.

Clinical efficacy of immunotherapy combined with chemotherapy in patients with advanced gastric cancer, its effect on nutritional status and Changes of peripheral blood T lymphocyte subsets.

OBJECTIVES: To evaluate the clinical efficacy of immunotherapy combined with chemotherapy in patients with advanced gastric cancer and its effect on nutritional status and changes of peripheral blood T lymphocyte subsets. METHODS: Sixty patients with locally advanced gastric cancer who were admitted by Affiliated Hospital of Hebei University from March 2020 to February 2021 were enrolled and randomly divided into two groups, with 30 cases in each group. The control group was treated with FOLFOX4 chemotherapy, while the experimental group was additively treated with cindilizumab on the basis of control group. The incidence of adverse reactions, clinical efficacy, improvement of nutritional and physical status, and changes in the levels of T lymphocyte subgroups in the two groups were compared and analyzed. RESULTS: The total effective rate was 70% in the experimental group, which was better than 43.3% of the control group (p=0.04). The improvement rate of performance status (ECOG) score and nutritional indicators in the experimental group was significantly better than that in the control group (p<0.05). Moreover, the indicators of CD3+, CD4+, CD4+/CD8+ in the experimental group were significantly higher than those in the control group after treatment, with statistically significant differences (CD3+, p=0.01; CD4 +, p= 0.02; CD4+/CD8+, p=0.01). CONCLUSION: Immunotherapy combined with chemotherapy has a significant effect on locally advanced gastric cancer patients, with significant improvement in physical strength and nutritional status, significant improvement in T lymphocyte function, and no obvious adverse reactions. It is worth promoting in clinical application.

Inducible T-cell co-stimulators regulate the proliferation and invasion of human hepatocellular carcinoma HepG2 cells.

BACKGROUND: This study determined the regulatory effects of inducible T-cell co-stimulators (ICOS) in human hepatocellular carcinoma HepG2 cells using a RNA interference (RNAi) technique. METHODS: A RNAi technique was used to knockdown the expression of ICOS. ICOS expression after knockdown was detected as mRNA and protein levels by RT-PCR and Western blot, respectively. A MTT colorimetric assay was used to detect cell proliferation, and the Transwell assay was used to detect cell invasion. Western blot was carried out to detect the level of Bcl-2, AKT, and PI3K protein expression in different groups. RESULTS: The proliferation of HepG2 cells were significantly decreased after ICOS siRNA transfection (EG group). Similarly, the results of the Transwell experiment showed that invasion of HepG2 cells in the EG group was clearly reduced compared to the negative control (NC) and blank control groups (CON). Western blot analysis showed that knockdown of ICOS expression reduced the levels of Bcl-2 and AKT, and also significantly up-regulated the level of PI3K phosphorylation (P < 0.01). CONCLUSION: Down-regulating ICOS expression in HepG2 cells suppressed cell proliferation and invasion. The underlying mechanism may be related to the expression of the downstream factor, PI3K/AKT.

Mechanical upcycling of single-use face mask waste into high-performance composites: An ecofriendly approach with cost-benefit analysis.

The COVID-19 pandemic created an unprecedented demand for PPE, with single-use face masks emerging as a critical tool in containing virus transmission. However, the extensive use and improper disposal of these single-use face masks, predominantly composed of non-biodegradable plastics, has exacerbated environmental challenges. This research presents an innovative method for mechanically upcycling PPEs used in medical sectors i.e. single use face masks. The study investigates a facile approach for reclamation of infection-free and pure polypropylene (PP) plastic from discarded single use face masks (W-PP) and blends it with various vegetable oil percentages (5, 10 and 20 %), resulting in a versatile material suitable for various applications. Melt flow index, rheological behaviour, DSC and FTIR were employed to investigate the effect of vegetable oil/radical initiator through chemical grafting on W-PP properties. The results demonstrate significant enhancements in the tensile strength and modulus of W-PP when blended with vegetable oil and a radical initiator. There was a marked increase in tensile strength (33 %) and strain (55 %) compared to untreated W-PP, rendering W-PP both robust and flexible. Furthermore, we employed this upcycled W-PP in the fabrication of glass fibre-reinforced composites, resulting in notable enhancements in both tensile strength and impact resistance. The upcycled W-PP demonstrates excellent potential for various applications, such as sheet forming and 3D printing, where the non-brittleness of plastics plays a pivotal role in manufacturing high-quality products. The cost-benefit analysis of this approach underscores the potential of upcycling PPE waste as a sustainable solution to mitigate plastic pollution and conserve valuable resources. The applications of this upcycled material span a wide range of industries, including automotive composites, packaging, and 3D printing.

Disruption of the transcription factor RBP-J results in osteopenia attributable to attenuated osteoclast differentiation.

The transcription factor recombination signal binding protein-Jκ (RBP-J) is the critical transcription factor downstream to all four mammalian Notch receptors. Although it has been reported that Notch signaling pathway is involved in bone remodeling, the importance of RBP-J in osteoclastogenesis has not been fully explored. To investigate the role of RBP-J in osteoclastogenesis, we conditionally deleted RBP-J systemically in bone marrow (BM) or specifically in macrophages. We found that disruption of RBP-J in BM resulted in an obvious decrease in trabecular bone mass associated with an increase in osteoclasts, leading to osteopenia. Disruption of RBP-J in macrophages phenocopied the phenotypes of RBP-J deletion in BM with respect to osteoclastogenesis, suggesting that the osteopenia in RBP-J deficient mice is essentially resulted from increased osteoclastogenesis. Furthermore, we found that RBP-J deletion in osteoclasts resulted in a dramatic increase in tartrate-resistant acid phosphatase expression. These findings demonstrate a negatively role of RBP-J in the differentiation of osteoclasts and suggest that Notch pathway may be a new therapeutic target for bone diseases related to increased osteoclastogenesis.

Identification of Pyrabactin resistance 1-like (PYL) genes in Brachypodium distachyon and functional characterization of BdPYL5.

Abscisic acid (ABA) is an endogenous phytohormone that plays an important role in regulating plant growth, development, and stress response. Pyrabactin resistance 1-like (PYR/PYL) proteins are ABA receptors and core components of ABA signalling in plants. This study identified nine PYL genes in the Brachypodium distachyon genome and they distribute on three chromosomes. Phylogenetical BdPYLs were classified into three clades. 81 protein-protein interactions between 9 BdPYLs and 9 BdPP2C proteins were predicted and 66 pairs were verified by yeast two-hybrid assay previously. Relatively, BdPYL genes are expressed in leaves at high level, and ABA and drought regulate their expression. A homologue of Arabidopsis PYL9, BdPYL5 was selected to overexpress in Arabidopsis to characterize its function. In general, overexpression of BdPYL5 enhanced ABA sensitivity and drought tolerance, implying its conserved function. Our study lays the foundation for further functional elucidation of BdPYL genes.

Case Report: A management strategy and clinical analysis of primary squamous cell carcinoma of the colon.

Primary colorectal squamous cell carcinoma (CSCC) is a rare pathological subtype. Currently, clinical data with regards to its prognosis and treatment is limited, and there is no optimal treatment method. The case presented involves a proficient mismatch repair (pMMR) and microsatellite-stable (MSS) Colorectal cancer (CRC) patient with squamous cell carcinoma (SCC) located transversely in the colon. Based on the imaging assessment, the tumor infiltration depth is classified as T4. After receiving 4 cycles of neoadjuvant treatment with oxaliplatin and capecitabine (XELOX), the patients were evaluated for partial response (PR) in 2 cycles and stable disease (SD) in 4 cycles. The patient underwent a right hemicolectomy and received postoperative paclitaxel/cisplatin (TC) adjuvant chemotherapy. After 23 months, a systemic examination revealed abdominal metastasis. A needle biopsy was conducted on the detected abdominal metastases, with the resulting pathology indicating the presence of metastatic SCC. The individual exhibited expression of programmed cell death ligand 1 (PD-L1) and a mutation in the TP53 gene. Considering the patient's disease recurrence based on medical history, a treatment plan was formulated. This involved Sintilimab plus Cetuximab and the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen. The patient received four cycles of treatment with an efficacy evaluation of SD- and seven cycles of treatment with an efficacy evaluation of SD+, which resulted in a progression-free survival (PFS) duration of 7 months. This case study presents the conventional XELOX chemotherapy protocol, which has shown limited effectiveness, and highlights the favorable results achieved by implementing the TC adjuvant chemotherapy regimen in individuals diagnosed with primary colonic SCC. Furthermore, combining immune checkpoint blockade (ICB) with other therapies for patients with advanced disease is anticipated to provide an extended duration of survival.

Serum exosomal microRNA-370-3p and microRNA-196a-5p are potential biomarkers for the diagnosis and prognosis of hepatocellular carcinoma.

INTRODUCTION: Evidence has shown that some microRNAs (miRNAs) play a role in tumorigenesis of hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the diagnostic and prognostic values of serum exosomal miR-370-3p and miR-196a-5p in patients with HCC. MATERIAL AND METHODS: Serum exosomes in 90 HCC patients were extracted and identified. Serum exosomal miR-370-3p and miR-196a-5p expression in HCC patients were detected. The diagnostic value of miR-370-3p and miR-196a- 5p, relationship between miR-370-3p and miR-196a-5p expression and clinicopathological features and prognosis of patients with HCC were analyzed. Relationship between miR-370-3p and miR-196a-5p expression and liver function indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in HCC patients were analyzed. The effects of miR-370-3p and miR-196a-5p on Huh-7 HCC cells' proliferation, invasion and migration were determined. RESULTS: Lower expression of miR-370-3p and higher expression of miR-196a-5p were found in serum exosomes of HCC patients. Serum exosomal miR-370-3p and miR-196a-5p were associated with tumor size, tumor grade and TNM stage as well as prognosis and liver function indices of HCC patients. Overexpressed miR-370-3p or silenced miR-196a-5p suppressed proliferation, invasion and migration of Huh-7 HCC cells. CONCLUSIONS: We suggest that miR-370-3p/miR-196a-5p in serum exosomes of HCC patients could be potential biomarkers for the diagnosis and prognosis of HCC.

Construction of a miRNA Signature Using Support Vector Machine to Identify Microsatellite Instability Status and Prognosis in Gastric Cancer.

Background: The specific role and prognostic value of DNA repair and replication-associated miRNAs in gastric cancer (GC) have not been clearly elucidated. Therefore, comprehensive analysis of miRNAs in GC is crucial for proposing therapeutic strategies and survival prediction. Methods: Firstly, clinical information and transcriptome data of TCGA-GC were downloaded from the database. In the entire cohort, we performed differential analysis in all miRNAs and support vector machine (SVM) was used to eliminate redundant miRNAs. Subsequently, we combined survival data and cox regression analysis to construct a miRNA signature in the training cohort. In addition, we used PCA, Kaplan-Meier, and ROC analysis to explore the prognosis value of risk score in the training and testing cohort. It is worth noting that multiple algorithms were used to evaluate difference of immune microenvironment (TME), microsatellite instability (MSI), tumor mutational burden (TMB), and immunotherapy in different risk groups. Finally, we investigated the potential mechanism about miRNA signature. Results: We constructed miRNA signature based on the following 4 miRNAs: hsa-miR-139-5p, hsa-miR-139-3p, hsa-miR-146b-5p, and hsa-miR-181a-3p. Univariate and multivariate Cox regression analyses suggested that risk score is a risk factor and an independent prognostic factor in GC patients. The AUC value of ROC analysis showed a robust prediction accuracy in each cohort. Moreover, significant differences in immune functions, immune cell content, immune checkpoint, MSI status, and TMB score were excavated in different groups distinguished by risk score. Finally, based on the above four miRNA target genes, we revealed that the signature was enriched in DNA repair and replication. Conclusion: We have developed a robust risk-formula based on 4 miRNAs that provides accurate risk stratification and prognostic prediction for GC patients. In addition, different risk subgroups may potentially guide the choice of targeted therapy.

CRISPR/Cas9­induced saturated mutagenesis identifies Rad51 haplotype as a marker of PARP inhibitor sensitivity in breast cancer.

Breast cancer treatment with poly(ADP­ribose)polymerase (PARP) inhibitors is currently limited to cells defective in the homologous recombination repair (HRR) pathway. The chemical inhibition of many HRR deficiency genes may sensitize cancer cells to PARP inhibitors. In the present study, Rad51, a central player in the HRR pathway, was selected to explore additional low variation and highly representative markers for PARP inhibitor activity. A CRISPR/Cas9­based saturated mutation approach for the Rad51 WALKER domain was used to evaluate the sensitivity of the PARP inhibitor olaparib. Five amino acid mutation sites were identified in olaparib­resistant cells. Two Rad51 haplotypes were assembled from the mutations, and may represent useful pharmacogenomic markers of PARP inhibitor sensitivity.

SEMA3D Plays a Critical Role in Peptic Ulcer Disease-Related Carcinogenesis Induced by H. pylori Infection.

BACKGROUND: Immune cell infiltration plays a critical role in regulating peptic ulcer disease (PUD) and gastrointestinal cancer (GC). However, regulators of the cell signaling hubs remain unclear. AIM: This study characterizes genes that are differentially expressed in PUD and GC tissue samples. Bioinformatics is used to define the immune-associated hub genes associated with the malignant transfer process of PUD to GC. METHODS: Total expression data from PUD and early-stage GC tissue samples were obtained from GEO and TCGA. Differentially expressed genes were assessed and immunological enrichment analysis was performed. Protein-protein interaction (PPI) and Cytoscape analysis were used together to identify the hub genes. CIBERSORT and COX analysis were used to analyze the differentially infiltrated immune cell landscapes and determine HR scores of the hub genes. RESULTS: Expression data identified 437 DEGs as common to both GC and PUD tissue. Of these, 49 immune-related DEGs were grouped by function, and seven hub genes were identified by PPI analysis. The NRP2 and SEMA3D genes were then selected for survival analysis. SEMA3D had a higher hazard ratio than NRP2 and was defined as the hub for PUD carcinogenesis. CONCLUSION: SEMA3D was characterized as the hub gene for PUD carcinogenesis.

Notch signaling contributes to the maintenance of both normal neural stem cells and patient-derived glioma stem cells.

BACKGROUND: Cancer stem cells (CSCs) play an important role in the development and recurrence of malignant tumors including glioma. Notch signaling, an evolutionarily conserved pathway mediating direct cell-cell interaction, has been shown to regulate neural stem cells (NSCs) and glioma stem cells (GSCs) in normal neurogenesis and pathological carcinogenesis, respectively. However, how Notch signaling regulates the proliferation and differentiation of GSCs has not been well elucidated. METHODS: We isolated and cultivate human GSCs from glioma patient specimens. Then on parallel comparison with NSCs, we inhibited Notch signaling using γ-secretase inhibitors (GSI) and assessed the potential functions of Notch signaling in human GSCs. RESULTS: Similar to the GSI-treated NSCs, the number of the primary and secondary tumor spheres from GSI-treated GSCs decreased significantly, suggesting that the proliferation and self-renewal ability of GSI-treated GSCs were attenuated. GSI-treated GSCs showed increased differentiation into mature neural cell types in differentiation medium, similar to GSI-treated NSCs. Next, we found that GSI-treated tumor spheres were composed of more intermediate progenitors instead of CSCs, compared with the controls. Interestingly, although inhibition of Notch signaling decreased the ratio of proliferating NSCs in long term culture, we found that the ratio of G2+M phase-GSCs were almost undisturbed on GSI treatment within 72 h. CONCLUSIONS: These data indicate that like NSCs, Notch signaling maintains the patient-derived GSCs by promoting their self-renewal and inhibiting their differentiation, and support that Notch signal inhibitor GSI might be a prosperous candidate of the treatment targeting CSCs for gliomas, however, with GSI-resistance at the early stage of GSCs cell cycle.

miR-183 Enhances Autophagy of GC Cells by Targeted Inhibition of mTOR.

OBJECTIVE: We investigated whether miR-183 played a role in regulating mTOR expression and influencing autophagy of GC cells. METHODS: Tumor tissues and paracancerous tissues were collected from GC patients to detect the expressions of miR-183, mTOR, autophagy-related proteins Beclin-1. SGC-7901 cells were cultured in vitro and divided into 5 groups: MiR-NC group, MiR-183 mimic group, si-NC group, small interfering RNA transfected (si)-mTOR group, miR-183 mimic + si-mTOR group, to compare the expression of mTOR, apoptosis rate and clonality in all groups, and detect the expressions of Beclin-1 under starvation condition. RESULTS: The expressions of miR-183, Beclin-1 in GC tissues were significantly decreased, and the expression of mTOR was significantly increased compared with those in paracancerous tissues. There was a targeted-regulating relationship between miR-183 and mTOR. Compared with GES-1 cells, miR-183 expression was decreased and mTOR expression was increased in SGC-7901 cells, and under starvation condition, the expressions of Beclin-1 were decreased. After transfected with miR-183 mimic and/or si-mTOR, the expression of mTOR in SGC-7901 cells was decreased significantly, the cell clonality was significantly reduced, apoptosis was increased significantly, and cell autophagy activity induced by starvation was significantly enhanced. CONCLUSION: miR-183 can influence the proliferation, apoptosis and autophagy of GC cells through targeted inhibition of mTOR expression.

XRCC2 Arg188His polymorphism and colorectal cancer risk: a meta-analysis.

OBJECTIVE: To investigate the potential correlation between the Arg188His (rs3218536) polymorphism of X-ray repair cross-complementing 2 (XRCC2) and colorectal cancer (CRC) risk, as the association remains unclear. METHODS: The CNKI, PubMed, EMBASE and Cochrane library databases were systematically searched for relevant studies published up to July 2021. Data were extracted from included studies, and analysed for pooled or subgroup odds ratios (ORs) with 95% confidence intervals (CIs) using STATA 12.0 software. RESULTS: Seven published studies were included. Pooled analysis revealed that the XRCC2 Arg188His polymorphism was associated with increased CRC risk (His versus Arg: OR 1.14, 95% CI 1.01, 1.29). Trial Sequential Analysis to test the power of the results showed that they were unreliable and the meta-analysis required additional studies. CONCLUSION: The current meta-analysis suggests that the XRCC2 Arg188His polymorphism may be a risk factor for CRC.

A HER2-mutant patient with late-stage duodenal adenocarcinoma benefited from anti-HER2 therapy and PD-1 inhibition: a case report.

Duodenal adenocarcinoma (DA) is a subtype of small bowel adenocarcinoma (SBA). Compared with gastrointestinal cancers such as colorectal cancer and gastric cancer, SBA is less common. For patients with advanced and metastatic DA, chemotherapies are usually extrapolated from colorectal cancer and gastric cancer but the therapeutic effects remain undefined. Herein, we reported a 50-year-old female patient whom was diagnosed as stage IV DA with metastasis to both lungs and retroperitoneal lymph nodes. The next generation sequencing (NGS) using a panel consisting of 168 cancer related genes revealed amplification of the HER2/ERBB2 gene which has been a well-recognized therapeutic target among various tumor types. The anti-HER2 targeted therapy trastuzumab was used in combination with XELOX (oxaliplatin and capecitabine) as the first line treatment. The patient achieved partial response (PR) and had progression-free survival (PFS) of six months. After progressive disease (PD), the patient started the second line treatment with trastuzumab and PD1 inhibitors and remained stable disease (SD) with PFS for three months. The use of trastuzumab in neoadjuvant and adjuvant settings have been reported in sporadic cases. To the best of our knowledge, it is the first report to use anti-HER2 therapy and PD-1 inhibition as systemic therapy for advanced DA patients.

MicroRNA-125b as a tumor suppressor by targeting MMP11 in breast cancer.

BACKGROUND: Breast cancer is a common type of tumor in women worldwide. MicroRNAs have been identified as regulators in many human cancers. The aim of this study was therefore to investigate the functional role of miR-125b in regulating breast cancer progression. METHODS: We used the StarBase database to investigate the expression of miRNA-125b in breast cancer and adjacent normal tissues. MMP11 3'-UTR construct and luciferase reporter assays was performed for target genes. Cell proliferation was evaluated by CCK-8 and colony formation assay. The migration and invasion were assessed by transwell assay. RESULTS: Luciferase reporter assays showed miRNA-125b directly targeted MMP11. miRNA-125b by transfection with its mimic in breast cancer cells significantly suppressed breast cancer cell proliferation and migration. Western blot revealed that overexpression of miRNA-125b substantially reduced MMP11 protein expression. We used the UALCAN database to investigate the expression of MMP11 in human breast cancer and adjacent normal tissues. In addition, we found that miRNA-125b spoiled MMP11 induced breast cancer cell proliferation and migration promotion effect. CONCLUSIONS: miRNA-125b mimic inhibited proliferation, migration, and invasion of breast cancer cells through targeting MMP11 protein.

Hyaluronic Acid Capped, Irinotecan and Gene Co-Loaded Lipid-Polymer Hybrid Nanocarrier-Based Combination Therapy Platform for Colorectal Cancer.

BACKGROUND: The current approach for treating colorectal cancer favors the use of drug and gene combination therapy, and targeted nano-systems are gaining considerable attention for minimizing toxicity and improving the efficacy of anticancer treatment. The aim of this study was to develop ligand-modified, irinotecan and gene co-loaded lipid-polymer hybrid nanocarriers for targeted colorectal cancer combination therapy. METHODS: Hyaluronic acid modified, irinotecan and gene co-loaded LPNs (HA-I/D-LPNs) were prepared using a solvent-evaporation method. Their average size, zeta potential, drug and gene loading capacity were characterized. The in vitro and in vivo gene transfection and anti-tumor ability of this nano-system were evaluated on colorectal cancer cells and mice bearing colorectal cancer model. RESULTS: HA-I/D-LPNs had a size of 182.3 ± 5.1, over 80% drug encapsulation efficiency and over 90% of gene loading capacity. The peak plasma concentration (Cmax) and half-life (T1/2) achieved from HA-I/D-LPNs were 41.31 ± 1.58 µg/mL and 12.56 ± 0.67 h. HA-I/D-LPNs achieved the highest tumor growth inhibition efficacy and the most prominent transfection efficiency in vivo. CONCLUSION: HA-I/D-LPNs exhibited the most remarkable tumor inhibition efficacy and best gene transfection efficiency in the tumor, which could prove the effects of the drug and gene combination therapy.