Normal Tissue Cell Lines Research Articles

MicroRNA-124-3p targets Sp1 transcription factor to regulate glioma progression in rats

Gliomas are the most prevalent malignancies of the central nervous system (CNS). Downregulation of microRNA‑124 (miR‑124) has been identified in glioma; however, its biological functions in glioma are not yet fully understood. Specificity protein 1 (SP1) is a type of transcription factor that is involved in cancer progression. In this study, we examined the targeting of Sp1 mRNA by miR-124-3p in a rat glioma model. After confirming and selecting the binding of Sp1 to miR-124 with the help of bioinformatics methods, adult male Wistar rats were used to induce glioma by microinjection of 1×106 C6 cells into the striatum area of brain. The rats were divided into 3 groups; intact, sham and glioma groups. The presence of glioma was confirmed 21days after implantation through histological analysis. The expression levels of miR-124 and SP1 genes in the experimental groups were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Our data showed that the expression of miR-124 was significantly downregulated in glioma group compared to the sham and intact group, while the expression of SP1 was significantly upregulated. We found that the expression levels of miR-124 and Sp1 were decreased and increased in C6 cell line compared to the normal brain tissue cell line, respectively. The results indicated that Sp1 was identified as a direct target of miR‑124 through luciferase reporter assays. In summary, this study demonstrated for the first time that miR-124 expression is downregulated and Sp1 expression is upregulated in an animal model of glioma, which, in turn, may be involved in the development of glioma brain cancer.

TRIM47 inhibits cisplatin chemosensitivity and endoplasmic reticulum stress-induced apoptosis of ovarian cancer cells

Ovarian cancer (OC) is the fifth most common cause of death in women worldwide. Chemoresistance is a key reason for treatment failure, causing high mortality. As a member of the tripartite motif-containing (TRIM) protein family, tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers. This study investigated the impact and mechanisms of TRIM47 on cisplatin (DDP) chemosensitivity and apoptosis in OC. OC cell viability was assessed with a cell counting kit-8 assay and OC cell apoptosis was assessed using flow cytometry, caspase-3 and caspase-9 activity, and Bax and Bcl-2 expression assays while gene and protein expression were assessed using qRT-PCR and Western blot assays. The expression of TRIM47 was significantly increased in both DDP-resistant tissues from patients with OC tissues and in cancer cell lines compared with that in normal tissue or parental cell lines. The increased level of TRIM47 correlated with poor prognosis in patients with OC. Functional assays demonstrated that TRIM47 promoted DDP resistance both in vitro and in vivo. The increased viability and reduced apoptosis of OC cells induced by TRIM47 can be rescued by the endoplasmic reticulum (ER) stress-inducer tunicamycin, suggesting that TRIM47 inhibits OC cell apoptosis by suppressing ER stress. Therefore, TRIM47 may be targeted as a therapeutic strategy for DDP resistance in OC.

The effect of 1-deoxynojirimycin isolated from logging residue of Bagassa guianensis on an in vitro cancer model

Introduction:Bagassa guianensis Aubl, a tree widely distributed in Brazil, significantly contributes to the furniture industry. Notably, it harbors the bioactive compound 1-deoxynojirimycin (1-DNJ), which is retrievable from timber residues and retains activity even days after wood extraction. This makes Bagassa guianensis a promising biological resource for anticancer therapy and pharmacology studies. This study delves into the in vitro antineoplastic actions of 1-DNJ, focusing on adenocarcinoma gastric cell lines (ACP02) and glioblastoma (A172).Methods: The effect of 1-DNJ on cell viability was evaluated after 72 hours of treatment in the ACP02 and A172 cell lines. We also assessed the effect of 1-DNJ on the pattern of cell migration, cell death, changes in the cell cycle by flow cytometry, the production of reactive oxygen, and its antioxidant capacity in the scavenging of free radicals.Results: Assessing cell viability after 72 h (about 3 days) of treatment reveals a remarkable reduction, particularly in glioblastoma cells (A172), exhibiting a lower IC50 compared to ACP02 and MRC5 (fibroblast derived from normal lung tissue) cell lines. This decreased viability correlates with reduced reactive oxygen species (ROS) production in both cell lines after the treatment with 1-DNJ. Furthermore, 1-DNJ induces cell cycle arrest, impedes cell migration, and prompts cell death in ACP02 and A172.Discussion: These findings support 1-DNJ as a potent antineoplastic agent, particularly efficacious against glioblastoma and gastric adenocarcinoma. Thus, unveiling the therapeutic potential of Bagassa guianensis Aubl for cancer treatment and expanding the horizons of bioeconomy applications.

Circ-ITCH inhibits bladder cancer progression through miR-184/FOXO3 axis.

This study aimed to explore the role of circ-ITCH in the progression of bladder cancer (BCa). Kaplan-Meier analysis was performed to evaluate the prognostic significance of miR-184 in bladder cancer. Clustering analysis compared miR-184 expression levels across various BCa cell lines. Cell Counting Kit-8 (CCK-8) and transwell assays were used to assess cell proliferation and migration. Dual-luciferase reporter assays were employed to examine the regulatory relationship among circ-ITCH, miR-184, and FOXO3. Western blot analysis was conducted to investigate the post-transcriptional regulation of the circ-ITCH/miR-184/FOXO3 axis. The study demonstrated a correlation between elevated miR-184 expression and poor prognosis in bladder cancer. Compared to SV-HUC, a normal bladder tissue cell line, most BCa cell lines exhibited increased miR-184 expression. Additionally, miR-184 was found to promote BCa cell progression. Importantly, circ-ITCH was identified as a natural sponge for miR-184 in BCa. Overexpression of circ-ITCH in BCa significantly reduced miR-184 expression, thereby inhibiting cell proliferation and migration. Moreover, FOXO3, a target of miR-184, is regulated by circ-ITCH. The suppression of FOXO3 by miR-184 was counteracted by circ-ITCH, which diminished the tumor-promoting effects of miR-184. This study underscores the pivotal role of the circ-ITCH/miR-184/FOXO3 axis in regulating BCa cell proliferation and migration. It introduces a potential therapeutic target for bladder cancer, suggesting that strategies like circ-ITCH overexpression and miR-184 inhibition could offer promising treatment options.

Integrated analysis of NET-DNA receptor CCDC25 in malignant tumors: Pan-cancer analysis.

Previously, it was reported that the coiled-coil domain containing 25 (CCDC25) plays a role in the formation of neutrophil extracellular traps (NETs). This study systematically analyzed the expression profiles of CCDC25 in 30 different types of cancer and one type of blood cancer, acute myeloid leukemia. The GTEx and CCLE databases were used to evaluate the distribution of CCDC25 expression in both normal tissue and cancer cell lines. A comparison was performed between normal tissue and tumor tissue to analyze the differential expression of CCDC25. We assessed the impact of CCDC25 on the clinical outlook in the TCGA pan-cancer data set by analyzing the Kaplan-Meier survival plot and conducting COX regression analysis. Moreover, the association between the expression levels of CCDC25 and the tumor microenvironment in multiple cancers was conducted. Additionally, the investigation also examined the link between CCDC25 and immune neoantigen, tumor mutational burden, microsatellite instability, mismatch repair genes (MMRs), HLA-related genes, and DNA methyltransferase (DNMT). CCDC25 was expressed in nearly all of the 31 normal tissues while exhibiting a moderate to low level of expression in cancer cell lines. While abnormal expression was detected in the majority of malignancies, there was no link found between elevated CCDC25 levels and overall survival, disease-free survival, recurrence-free survival, and disease-free intervalin the TCGA comprehensive cancer data set. Nevertheless, the expression of CCDC25 exhibited a notable link with the infiltration levels of activated CD4 memory T cells, quiescent mast cells, dendritic cells in an activated state, T cells that assist in follicle development, M2 macrophages, and neutrophils in various tumors. In most cancers, the results indicate that there is no link between CCDC25 and prognosis. However, CCDC25 can be targeted for therapeutic purposes concerning metastasis and immune infiltration.

MIR-147B Regulated Proliferation and Apoptosis of Gastric Cancer Cells by Targeting CPEB2 Via the PTEN Pathway.

The present study has been performed to illustrate the role and mechanism of microRNA-147b (miR-147b) in the cellular viability and apoptosis of gastric cancer (GC) cells. The GC tissues of 50 patients with complete data and the adjacent tissues were selected from Shanxi Cancer Hospital, and 3 pairs of tissues were randomly selected for microarray detection of high-expressing microRNAs. The expressions of miR-147b were quantified in numerous GC cell lines, i.e., BGC-823, SGC-7901, AGS, MGC-803 and MKN-45, normal tissue cell lines and 50 pairs of gastric cancer tissues. Moreover, two cell lines of miR-147b high-expressing used PCR quantitative analysis were selected for transfection experiments. The differentially expressed miR-147b was screened from 3 pairs of samples by miRNA chip. The expression ofmiR-147b was found highly expressed in gastric cancer tissues of 50 pairs of gastric cancer and adjacent tissues. The miR-147b found in diverse range in each of GC cell line. Therefore, two cell lines, BGC-823 and MGC-803, with relatively high expression levels of miR-147b were selected for further analysis and research. Scratch analysis results showed that compared with miR-147b NC, the miR-147b inhibitor group inhibited GC cell growth and reduced cell migration. The early apoptosis of MGC-803, and BGC-823 cells was enhanced by miR-147b inhibitor. miR-147b inhibitor significantly repressed the proliferation of BGC-823 and MGC-803 cells. Our study showed that the high expression of miR-147b is positively correlated with the occurrence and development of gastric cancer.

Identification and validation of biomarkers for epithelial-mesenchymal transition-related cells to estimate the prognosis and immune microenvironment in primary gastric cancer by the integrated analysis of single-cell and bulk RNA sequencing data.

The epithelial-mesenchymal transition (EMT) is associated with gastric cancer (GC) progression and immune microenvironment. To better understand the heterogeneity underlying EMT, we integrated single-cell RNA-sequencing (scRNA-seq) data and bulk sequencing data from GC patients to evaluate the prognostic utility of biomarkers for EMT-related cells (ERCs), namely, cancer-associated fibroblasts (CAFs) and epithelial cells (ECs). scRNA-seq data from primary GC tumor samples were obtained from the Gene Expression Omnibus (GEO) database to identify ERC marker genes. Bulk GC datasets from the Cancer Genome Atlas (TCGA) and GEO were used as training and validation sets, respectively. Differentially expressed markers were identified from the TCGA database. Univariate Cox, least-absolute shrinkage, and selection operator regression analyses were performed to identify EMT-related cell-prognostic genes (ERCPGs). Kaplan-Meier, Cox regression, and receiver-operating characteristic (ROC) curve analyses were adopted to evaluate the prognostic utility of the ERCPG signature. An ERCPG-based nomogram was constructed by integrating independent prognostic factors. Finally, we evaluated the correlations between the ERCPG signature and immune-cell infiltration and verified the expression of ERCPG prognostic signature genes by in vitro cellular assays. The ERCPG signature was comprised of seven genes (COL4A1, F2R, MMP11, CAV1, VCAN, FKBP10, and APOD). Patients were divided into high- and low-risk groups based on the ERCPG risk scores. Patients in the high-risk group showed a poor prognosis. ROC and calibration curves suggested that the ERCPG signature and nomogram had a good prognostic utility. An immune cell-infiltration analysis suggested that the abnormal expression of ERCPGs induced the formation of an unfavorable tumor immune microenvironment. In vitro cellular assays showed that ERCPGs were more abundantly expressed in GC cell lines compared to normal gastric tissue cell lines. We constructed and validated an ERCPG signature using scRNA-seq and bulk sequencing data from ERCs of GC patients. Our findings support the estimation of patient prognosis and tumor treatment in future clinical practice.

LINC01023 Promotes the Hepatoblastoma Tumorigenesis via miR-378a-5p/WNT3 Axis.

Hepatoblastoma is the most common type of hepatic tumors occurring in children between 0 and 5years. And the exact pathophysiology of the disease is still mysterious. Accumulating studies on LncRNA have shown its pivotal role in the development and progression of distinct human cancers. However, the role of LINC01023 in hepatoblastoma is unknown. The relative expression of LINC01023, miR-378a-5p, and Wnt3 on hepatoblastoma tissue and cell lines was determined by quantitative polymerase chain reaction (qRT-PCR). The effect of LINC01023 downregulation and upregulation on cell proliferation, colony formation and apoptosis activities in HUH6 and HepG2 Cells was assessed by CKK8, clonogenic and flow cytometry analysis, respectively. Dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down were performed to confirm the interaction between LINC01023 and miR-378a-5p. Similarly, Dual luciferase assay was performed to confirmed the interaction between Wnt3 and miR-378a-5p. The xenograft tumorgenicity test was performed to elucidate the tumorgenicity potential of LINC01023. LINC01023 was significantly upregulated in hepatoblastoma tissue and cell lines rather than in adjacent normal hepatic tissue and QSG7701 cell lines. LINC01023 silencing attenuated cell proliferation, colony formation and increased cell apoptosis. Conversely, LINC01023 upregulation results in significant increase in cell proliferation, and colony formation activities however, a significant reduction in apoptosis activity was reported. Interaction between the LINC01023 and WNT3 was confirmed by dual luciferase assay. Xenograft animal tumorgenicity test confirmed the in-vivo tumorigenesis potential of LINC01203. To the best of our knowledge, this study is the first study demonstrating the role of LINC01023 in hepatoblastoma tumorigenesis through the LINC01023/miR-378a-5p/Wnt3 axis. It could be a potential therapeutic target and a prognostic biomarker in hepatoblastoma.

Circular ribonucleic acid circ-FADS2 promotes colorectal cancer cell proliferation and invasion by regulating miR-498/S100A16.

The aim of this study is to examine the role and functional mechanism of circ-FADS2 in colorectal cancer (CRC). The levels of expression of circ-FADS2 were detected in 48 patients with CRC and their paired normal tissue samples and cell lines (SW480, SW620, HCT116, HT29, and NCM460) using quantitative real-time polymerase chain reaction (qRT-PCR). Circ-FADS2 was then silenced in SW480 and HT29 cells using two small interfering ribonucleic acids. Themolecular mechanism of circ-FADS2 in CRC progression and migration was then examined by sponging miR-498 and promoting S100A16 expression. After this, the expression of miR-498 and S100A16 in CRC tissues was analyzed using a qRT-PCR. In results: circ-FADS2 was found to be significantly upregulated in CRC tissues, when compared with paired normal tissues. Higher circ-FADS2 expression was associated with advanced stages, lymphatic metastasis, and reduced overall survival (OS). In addition, silencing circ-FADS2 markedly inhibited the proliferation and invasion of CRC and increased the percentage of cancer cells in the G1 phase in vitro. Reducing circ-FADS2 decreased SW480 cell proliferation in vivo. By inhibiting miR-498 expression, circ-FADS2 promoted S100A16 expression leading to the activation of the AKT pathway, resulting in CRC progression. We conclude that Circ-FADS2 expression was upregulated in CRC tissues and cells and was found to be correlated with advanced cancer, metastasis, and poor OS. A study of the molecular mechanism suggests that a circ-FADS2/miR-498/S100A16/AKT signaling cascade may be a potential therapeutic target for the treatment of CRC.

MiR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis.

The aim of this study was to verify the biological function of miR-1273h-5p in gastric cancer (GC) and its underlying mechanisms. The differential expression of microRNAs between GC and tumor-adjacent normal tissues was detected using microarrays, miR-1273h-5p, and chemokine (C-X-C motif) ligand 12 (CXCL12) mRNA, and protein levels were evaluated using polymerase chain reaction and Western blotting methods, cell proliferation, apoptosis, migration, and invasion were determined by CCK-8, flow cytometry, and transwell assay. Compared to tumor-adjacent normal tissue and gastric epithelial mucosa cell line cells, miR-1273h-5p was significantly downregulated in tissues and cells of GC. The overexpression of miR-1273h-5p could inhibit cell proliferation, migration, invasion, and promote cell apoptosis; in contrast, inhibition of miR-1273h-5p expression could reverse this process. Moreover, a significant upregulation of CXCL12 was observed when the miR-1273h-5p was downregulated in GC cells. Additionally, miR-1273h-5p significantly reduces tumor volume and weight. Thus, this study suggests that miR-1273h-5p regulates cell proliferation, migration, invasion, and apoptosis during GC progression by directly binding to CXCL12 mRNA 3′-untranslational regions, which may be a novel diagnostic and therapeutic target in GC.

The regulating role of miR-494 on HCCR1 in cervical cancer cells.

This study focused on miR-494 inhibiting the proliferation, migration and invasion of cervical cancer cells by regulating HCCR1. During the study, 30 pairs of primary cervical cancer tissues and adjacent tissues diagnosed by pathology were collected, and then placed in a cryopreservation tube, immediately placed in liquid nitrogen to freeze, and then moved to a -80 °C refrigerator for storage until use. They were dipped with crystal violet staining solution for 20 minutes, washed 3 times with PBS, and dried at room temperature. The polycarbonate film on the chamber was gently cut, placed on a glass slide, and covered with neutral resin. The number of cells in 5 random fields was counted under a microscope, and the differences between the groups were compared. The qRT-PCR results showed that compared with the normal cervical tissue cell line HCCR1, the expression levels of miR-494 in cervical cancer cell lines HCCR1 and C-33A were significantly reduced. Compared with the transfection of mimics NC, the level of HCCR1mRNA and protein decreased significantly when transfected with miRNA-494mimics (P <0.05); compared with the transfection of inhibitor NC, the level of HCCR1 mRNA and protein increased significantly when transfected with miRNA-494 inhibitor (P <0.05).

MiR-325-3p functions as a suppressor miRNA and inhibits the proliferation and metastasis of glioma through targeting FOXM1

Glioma is a malignant brain tumor exhibiting high levels of proliferation and metastasis, and these have been related to its poor prognosis and high mortality rate. MicroRNA (miRNA)-325-3p exhibits tissue-specific expression profiles and is aberrantly expressed in multiple types of malignant tumors. Our research focuses on determining the function and mechanism of action of miR-325-3p in glioma. The relative expression levels of miR-325-3p in glioma tumor tissues and cell lines were verified by qRT-PCR. The effect of 325-3p on glioma tumor cell behavior was assessed using CCK-8 assays, EDU staining, colony formation assays, flow cytometry, transwell invasion assays, and a xenograft model. In addition, we searched for miR-325-3p targets, and their potential mechanism of action was demonstrated using a reporter assay and rescue experiments. Results showed that the expression levels of miR-325-3p in glioma cancer tissues and tumor cell lines were significantly lower than that of normal paired adjacent tissue or normal cell lines. Functional experiments illustrated that tumor proliferation, migration and invasion were suppressed via upregulation of miR-325-3p. To assess whether FOXM1 is a target of miR-325-3p, we examined this hypothesis using a luciferase report assay and then found that miR-325-3p could modulate the expression of FOXM1. Furthermore, the functional role of miR-325-3p was also confirmed in a xenograft model using nude mice. Together, our data demonstrated that in glioma, miR-325-3p may inhibit cancer cell growth through the suppression of FOXM1 and could be a promising new target for treating this type of brain cancer.

MiR‑497/MIR497HG inhibits glioma cell proliferation by targeting CCNE1 and the miR‑588/TUSC1 axis.

Emerging evidence has shown that microRNA (miR)-497 serves pivotal roles in tumorigenesis, cancer progression, metastasis and chemotherapy resistance in several types of cancer. In the present study, the expression and biological functions of miR-497 host gene (MIR497HG) were investigated in glioma tissue. The expression levels of miR-497 and MIR497HG were measured in glioma, adjacent non-cancerous and normal brain tissue and their association with the prognosis of patients with glioma were analyzed. The biological roles of miR-497 and MIR497HG were investigated in glioma cell lines. In addition, bioinformatics analysis, luciferase reporter assay and functional experiments were performed to identify and validate the downstream targets of miR-497 or MIR497HG. The expression levels of miR-497 and MIR497HG were downregulated in glioma tissue and cell lines compared with those in adjacent non-cancerous and normal brain tissue and normal human cortical neuron cell line. Patients with low miR-497 or MIR497HG expression levels exhibited a poor prognostic outcome. In addition, forced overexpression of miR-497 or MIR497HG significantly inhibited the proliferation and cell cycle progression of glioma cell lines. Furthermore, the results indicated that miR-497 and MIR497HG exerted their biological functions by direct targeting of cyclin E1 and miR-588/tumor suppressor candidate 1. In summary, the data indicated that miR-497 and MIR497HG served as tumor suppressors and may be used as potential therapeutic targets and prognostic biomarkers in glioma.

TCPP-Isoliensinine Nanoparticles for Mild-Temperature Photothermal Therapy.

PurposePhotothermal therapy (PTT) is promising for the treatment of tumors due to its advantages including minimally invasive, easy implementation and selective localized treatment. However, single PTT suffers from several limitations, such as constrained light penetration and low delivery efficiency, typically leading to heterogeneous heating and incomplete elimination of cancer cells. Therefore, combination of PTT with other therapies, eg, chemotherapy is desirable in order to achieve synergistic effects in cancer treatment.MethodsHere, we designed a new type of TCPP-Iso combined nanoparticle for synergetic therapy for breast cancer. Specifically, photothermal agent tetra(4-carboxyphenyl) porphine (TCPP) and anti-cancer drug isoliensinine (Iso) were encapsulated in PEG-b-PLGA polymeric nanoparticles through a precipitation process.ResultsThe obtained NPs displayed well-controlled size and high stability over time. Tuning TCPP-Iso/polymer ratio, or total concentration of drug and polymers led to increased hydrodynamic radius of NPs from 65 to 108 nm without disturbing the narrow size distribution. Besides, the formed NPs showed a consequently cumulative release of TCPP and of Iso. The temperature elevation ability of both TCPP NPs and TCPP-Iso NPs was TCPP-concentration dependent. Solutions of TCPP NPs that contained equivalent amount of TCPP with respect to TCPP-Iso NPs, presented the same trend and exhibited non-obvious difference in temperature elevation under certain laser power. The viability of MDA-MB-231 cells treated with TCPP-Iso NPs could be inhibited effectively at a relatively mild temperature (42–43°C) compared to the other groups, which may minimize heat damage to the surrounding healthy tissues.ConclusionThe results indicate that the TCPP-Iso combined NPs showed hardly any toxicity to normal tissue cell line, but displayed an efficient synergistic effect for killing cancer cells under laser irradiation. Our study demonstrates that the successful combination of TCPP and Iso realized a synergistic therapy effect at a relatively mild temperature, and the insights obtained here shall be helpful for designing new combined PTT agents for cancer treatment.

Shugoshin 2 is a biomarker for pathological grading and survival prediction in patients with gliomas

Glioblastomas are the most common type of adult primary brain neoplasms. Clinically, it is helpful to identify biomarkers to predict the survival of patients with gliomas due to its poor outcome. Shugoshin 2 (SGO2) is critical in cell division and cell cycle progression in eukaryotes. However, the association of SGO2 with pathological grading and survival in patients with gliomas remains unclear. We analyzed the association between SGO2 expression and clinical outcomes from Gene Expression Omnibus (GEO) dataset profiles, The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA). SGO2 mRNA and protein expression in normal brain tissue and glioma cell lines were investigated via quantitative RT-PCR, Western blot, and IHC staining. The roles of SGO2 in proliferation, migration, and apoptosis of GBM cells were studied with wound-healing assay, BrdU assay, cell cycle analysis, and JC-1 assay. The protein–protein interaction (PPI) was analyzed via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). SGO2 mRNA expression predicted higher grade gliomas than non-tumor brain tissues. Kaplan–Meier survival analysis showed that patients with high-grade gliomas with a higher SGO2 expression had worse survival outcomes. SGO2 mRNA and protein expression were upper regulated in gliomas than in normal brain tissue. Inhibition of SGO2 suppressed cell proliferation and migration. Also, PPI result showed SGO2 to be a potential hub protein, which was related to the expression of AURKB and FOXM1. SGO2 expression positively correlates with WHO pathological grading and patient survival, suggesting that SGO2 is a biomarker that is predictive of disease progression in patients with gliomas.

TPE based aggregation induced emission fluorescent sensors for viscosity of liquid and mechanical properties of hydrogel

Two amphiphilic TPE E / Z isomers with aggregation induced emission (AIE) property have been synthesized and characterized. The logarithmic fluorescent intensity of the two molecules was in positive relationship with logarithmic viscosity of liquid. To note, the Z -TPE isomer exhibited more sensitivity in the viscosity of liquid sensing in comparison with the corresponding E -TPE counterpart (around 1.80 folds). Furthermore, two molecules could be used as fluorescent sensors for mechanical properties (viscosity and storage modulus) of hydrogel as well. In addition, two sensors displayed low cytotoxicity in normal tissue cell line (L929) within the concentration range of 2–10 µmol/L. These results potentially promised their applications as fluorescent sensors for mechanical properties in the fields of biological and biomedical. Amphiphilic tetraphenyl ethylene molecules (E-TPE and Z-TPE) realized fluorescent sensing of liquid viscosity and mechanical properties (viscosity and storage modulus).

ARID4B Knockdown Suppresses PI3K/AKT Signaling and Induces Apoptosis in Human Glioma Cells.

PurposeGlioblastoma multiforme is a highly malignant primary brain cancer with a poor prognosis. We recently reported that ARID4B could potentially serve as a biomarker associated with poor survival in glioma patients. However, the function of ARID4B in human gliomas remains unclear. The aim of this study is to investigate the molecular cell biology role of ARID4B in human glioma cells.Materials and MethodsGene Expression Omnibus (GEO) and Human Protein Atlas (HPA) datasets were analyzed for the expression of ARID4B in WHO pathological grading, overall survival and immunohistochemical staining. Using quantitative RT-PCR and Western blotting, those findings were confirmed in normal brain tissue and glioma cell lines. ARID4B knockdown was conducted via lentivirus-based transfection of small hairpin RNA in human glioma cells to investigate cell proliferation, cell cycle, and apoptosis.ResultsIn the present study, our analysis of GEO datasets showed that ARID4B mRNA expression is higher in WHO grade IV tumors (n = 81) than in non-tumor control tissue (n = 23, P <0.0001). ARID4B knockdown suppressed glioma cell proliferation and induced G1 phase arrest via the PI3K/AKT pathway. It also increased expression of HDAC1, leading to higher acetyl-p53 and acetyl-H3 levels and reduced glioma cell migration and invasion. These effects were mediated via downregulation of AKT pathway components, including p-mTOR, p-PI3K and p-AKT. ARID4B knockdown also led to downregulation of Cyclin D1, which increased apoptosis in human glioma cells.ConclusionThese findings that ARID4B expression correlates positively with WHO pathologic grading in glioma. ARID4B knockdown suppresses PI3K/AKT signaling and induces apoptosis in human glioma cells. These results suggests that ARID4B acts as an oncogene in human gliomas.

Increase in non-professional phagocytosis during the progression of cell cycle.

Homotypic or heterotypic internalization of another, either living or necrotic cell is currently in the center of research interest. The active invasion of a living cell called entosis and cannibalism of cells by rapidly proliferating cancers are prominent examples. Additionally, normal healthy tissue cells are capable of non-professional phagocytosis. This project studied the relationship between non-professional phagocytosis, individual proliferation and cell cycle progression. Three mesenchymal and two epithelial normal tissue cell lines were studied for homotypic non-professional phagocytosis. Homotypic dead cells were co-incubated with adherent growing living cell layers. Living cells were synchronized by mitotic shake-off as well as Aphidicolin-treatment and phagocytotic activity was analyzed by immunostaining. Cell cycle phases were evaluated by flow cytometry. Mesenchymal and epithelial normal tissue cells were capable of internalizing dead cells. Epithelial cells had much higher non-professional phagocytotic rates than mesenchymal cells. Cells throughout the entire cell cycle were able to phagocytose. The phagocytotic rate significantly increased with progressing cell cycle phases. Mitotic cells regularly phagocytosed dead cells, this was verified by Nocodazole and Colcemid treatment. Taken together, our findings indicate the ability of human tissue cells to phagocytose necrotic neighboring cells in confluent cell layers. The origin of the cell line influences the rate of cell-in-cell structure formation. The higher cell-in-cell structure rates during cell cycle progression might be influenced by cytoskeletal reorganization during this period or indicate an evolutionary anchorage of the process. Recycling of nutrients during cell growth might also be an explanation.

MiR-130a-3p suppresses colorectal cancer growth by targeting Wnt Family Member 1 (WNT1)

ABSTRACT The microRNA miR-130a-3p (miR-130a-3p) has anti-tumor activity against numerous cancer types. Further, miR-130a-3p may target Wnt signaling, which is a critical pathway regulating tumorigenesis. Functions of miR-130a-3p in colorectal cancer (CRC) and contributions of Wnt1 pathway modulation, however, have not been examined, hence the exploration on these two aspects. In this study, in comparison with normal controls, both CRC tissue and multiple CRC cell lines showed downregulated miR-130a-3p. MiR-130a-3p overexpression contributed to a decrease in CRC cell proliferation. Additionally, its overexpression also caused reduced expression of WNT Family Member 1 (WNT1) and downstream WNT pathway factors c-myc and cyclin D1. Dual-luciferase assay revealed WNT1 as a direct target of miR-130a-3p, and further the inhibitory effect of miR-130a-3p on c-myc and cyclin D1 was proved to be reversed by overexpressed WNT1. Collectively, miR-130a-3p inhibits CRC growth by directly targeting WNT1, and miR-130a-3p and WNT1 pathway-associated factors are defined as potential targets for CRC treatment.

Long non‑coding RNA ZFPM2‑AS1 promotes colorectal cancer progression by sponging miR‑137 to regulate TRIM24.

Accumulating evidence indicates that long non-coding RNAs (lncRNAs) may serve essential roles during tumorigenesis of colorectal cancer (CRC). The lncRNA ZFPM2-AS1 was observed to be involved in the progression of numerous types of cancer, such as lung adenocarcinoma and cervical cancer. The aim of the present study was to investigate the expression levels and function of ZFPM2-AS1 in CRC. Expression levels of ZFPM2-AS1 in tissue and CRC cells were measured by reverse transcription-quantitative PCR. Furthermore, cell proliferation and Transwell assays were conducted to investigate the functional role of ZFPM2-AS1 in vitro. In addition, bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation assay and western blotting were performed to explore the possible underlying mechanism. The expression levels of ZFPM2-AS1 were significantly upregulated in tissue samples from patients with CRC and CRC cell lines compared with normal tissue and normal human colorectal mucosa cell line. Notably, the upregulation of ZFPM2-AS1 was significantly associated with tumor size, histological differentiation, lymph node metastasis and TNM stage. In addition, ZFPM2-AS1 knockdown significantly inhibited cell proliferation, migration and invasion compared with the control group in vitro. Moreover, it was found that ZFPM2-AS1 positively regulated tripartite motif containing 24 (TRIM24) expression by sponging miR-137. In conclusion, the present study indicated that ZFPM2-AS1 may serve as an oncogene in CRC by regulating the miR-137/TRIM24 axis.