Circular RNAs and host genes act synergistically in regulating cellular processes and functions in skeletal myogenesis.

Circular RNAs (circRNAs) are post-transcriptional regulators generated from backsplicing of pre-mRNAs of host genes. A major circRNA regulatory mechanism involves microRNA (miRNA) sequestering, relieving miRNA-blocked mRNAs for translation and functions. To investigate possible circRNA-host gene relationship, skeletal myogenesis is chosen as a study model for its developmental importance and for readily available muscle tissues from farm animals for studies at different myogenic stages.

Circular RNA ZNF800 (hsa_circ_0082096) regulates cancer stem cell properties and tumor growth in colorectal cancer.

Background: Cancer stem cells form a rare cell population in tumors that contributes to metastasis, recurrence and chemoresistance in cancer patients. Circular RNAs (circRNAs) are post-transcriptional regulators of gene expression that sponge targeted microRNA (miRNAs) to affect a multitude of downstream cellular processes. We previously showed in an expression profiling study that circZNF800 (hsa_circ_0082096) was up-regulated in cancer stem cell-enriched spheroids derived from colorectal cancer (CRC) cell lines.

E7050 Suppresses the Growth of Multidrug-Resistant Human Uterine Sarcoma by Inhibiting Angiogenesis via Targeting of VEGFR2-Mediated Signaling Pathways.

E7050 is an inhibitor of VEGFR2 with anti-tumor activity; however, its therapeutic mechanism remains incompletely understood. In the present study, we aim to evaluate the anti-angiogenic activity of E7050 in vitro and in vivo and define the underlying molecular mechanism. It was observed that treatment with E7050 markedly inhibited proliferation, migration, and capillary-like tube formation in cultured human umbilical vein endothelial cells (HUVECs).

Circular RNA- and microRNA-Mediated Post-Transcriptional Regulation of Preadipocyte Differentiation in Adipogenesis: From Expression Profiling to Signaling Pathway.

Adipogenesis is an indispensable cellular process that involves preadipocyte differentiation into mature adipocyte. Dysregulated adipogenesis contributes to obesity, diabetes, vascular conditions and cancer-associated cachexia. This review aims to elucidate the mechanistic details on how circular RNA (circRNA) and microRNA (miRNA) modulate post-transcriptional expression of targeted mRNA and the impacted downstream signaling and biochemical pathways in adipogenesis.

The MicroRNA-signaling-peroxisome proliferator-activated receptor gamma connection in the modulation of adipogenesis: bioinformatics projection on chicken.

Meat quality and nutritional value hinge on many factors, including fat content in the adipose tissue. In the adipogenesis process, stem cells are first committed to become preadipocytes, followed by preadipocyte differentiation. In the later event, peroxisome proliferator activated receptor gamma (PPARγ) is the gateway through which adipogenic genes are activated.

MicroRNA-362 negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling to suppress cell migration and invasion.

Cell migration and invasion are modulated by epithelial-to-mesenchymal transition (EMT) and the reverse MET process. Despite the detection of microRNA-362 (miR-362, both the miR-362-5p and -3p species) in cancers, none of the identified miR-362 targets is a mesenchymal or epithelial factor to link miR-362 with EMT/MET and metastasis. Focusing on the TGF-β/SMAD signaling pathway in this work, luciferase assays and western blot data showed that miR-362 targeted and negatively regulated expression of SMAD4 and E-cadherin, but not SNAI1, which is regulated by SMAD4.

Mapping a Circular RNA-microRNA-mRNA-Signaling Regulatory Axis That Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells.

Spheroidal cancer cell cultures have been used to enrich cancer stem cells (CSC), which are thought to contribute to important clinical features of tumors. This study aimed to map the regulatory networks driven by circular RNAs (circRNAs) in CSC-enriched colorectal cancer (CRC) spheroid cells. The spheroid cells established from two CRC cell lines acquired stemness properties in pluripotency gene expression and multi-lineage differentiation capacity.

Oxidative Stress Down-Regulates MiR-20b-5p, MiR-106a-5p and E2F1 Expression to Suppress the G1/S Transition of the Cell Cycle in Multipotent Stromal Cells.

Oxidative stress has been linked to senescence and tumorigenesis via modulation of the cell cycle. Using a hydrogen peroxide (HO)-induced oxidative stress-induced premature senescence (OSIPS) model previously reported by our group, this study aimed to investigate the effects of oxidative stress on microRNA (miRNA) expression in relation to the G1-to-S-phase (G1/S) transition of the cell cycle and cell proliferation. On global miRNA analysis of the OSIPS cells, twelve significantly up- or down-regulated miRNAs were identified, the target genes of which are frequently associated with cancers.

Incomplete cellular reprogramming of colorectal cancer cells elicits an epithelial/mesenchymal hybrid phenotype.

Background: Induced pluripotency in cancer cells by ectopic expression of pluripotency-regulating factors may be used for disease modeling of cancers. MicroRNAs (miRNAs) are negative regulators of gene expression that play important role in reprogramming somatic cells. However, studies on the miRNA expression profile and the expression patterns of the mesenchymal-epithelial transition (MET)/epithelial-mesenchymal transition (EMT) genes in induced pluripotent cancer (iPC) cells are lacking.

miR-524-5p of the primate-specific C19MC miRNA cluster targets TP53IPN1- and EMT-associated genes to regulate cellular reprogramming.

Background: Introduction of the transcription factors Oct4, Sox2, Klf4, and c-Myc (OSKM) is able to 'reprogram' somatic cells to become induced pluripotent stem cells (iPSCs). Several microRNAs (miRNAs) are known to enhance reprogramming efficiency when co-expressed with the OSKM factors. The primate-specific chromosome 19 miRNA cluster (C19MC) is essential in primate reproduction, development, and differentiation.

Oncostatin M-Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary Fibrosis Through Paracrine Effects of the Hepatocyte Growth Factor.

Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs.

Selective activation of miRNAs of the primate-specific chromosome 19 miRNA cluster (C19MC) in cancer and stem cells and possible contribution to regulation of apoptosis.

Background: The human chromosome 19 miRNA cluster (C19MC) of 43 genes is a primate-specific miRNA cluster that may have biological significance in the genetic complexity of the primate. Despite previous reports on individual C19MC miRNA expression in cancer and stem cells, systematic studies on C19MC miRNA expression and biological functions are lacking.

Results: Cluster-wide C19MC miRNA expression profiling by microarray analysis showed wholesome C19MC activation in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs).

Risk factors associated with abdominal obesity in suburban adolescents from a Malaysian district.

Introduction: We aimed to determine the risk factors associated with abdominal obesity (AO) in suburban adolescents.

Methods: This cross-sectional study included adolescents aged 15-17 years from five randomly selected secondary schools in the Hulu Langat district of Selangor state, Malaysia. Waist circumference (WC) was measured at the midpoint between the lower margin of the last palpable rib and the top of the iliac crest.

Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model.

Chronic obstructive pulmonary disease (COPD) is a sustained blockage of the airways due to lung inflammation occurring with chronic bronchitis and/or emphysema. Progression of emphysema may be slowed by vascular endothelial growth factor A (VEGFA), which reduces apoptotic tissue depletion. Previously, authors of the present report demonstrated that cis-resveratrol (c-RSV)-induced heat-shock protein 70 (HSP70) promoter-regulated VEGFA expression promoted neovascularization of genetically modified mesenchymal stem cells (HSP-VEGFA-MSC) in a mouse model of ischemic disease.

Hypoxia-preconditioned mesenchymal stem cells attenuate bleomycin-induced pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis is a progressive diffuse parenchymal lung disorder of unknown etiology. Mesenchymal stem cell (MSC)-based therapy is a novel approach with great therapeutic potential for the treatment of lung diseases. Despite demonstration of MSC grafting, the populations of engrafted MSCs have been shown to decrease dramatically 24 hours post-transplantation due to exposure to harsh microenvironments.

Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol promotes angiogenesis in a mouse model.

Several studies of stem cell-based gene therapy have indicated that long-lasting regeneration following vessel ischemia may be stimulated through VEGFA gene therapy and/or MSC transplantation for reduction of ischemic injury in limb ischemia and heart failure. The therapeutic potential of MSC transplantation can be further improved by genetically modifying MSCs with genes which enhance angiogenesis following ischemic injury. In the present study, we aimed to develop an approach in MSC-based therapy for repair and mitigation of ischemic injury and regeneration of damaged tissues in ischemic disease.

Expression profile and down-regulation of argininosuccinate synthetase in hepatocellular carcinoma in a transgenic mouse model.

Background: Argininosuccinate synthetase (ASS) participates in urea and nitric oxide production and is a rate-limiting enzyme in arginine biosynthesis. Regulation of ASS expression appears complex and dynamic. In addition to transcriptional regulation, a novel post-transcriptional regulation affecting nuclear precursor RNA stability has been reported.

Wnt pathway activation and ABCB1 expression account for attenuation of proteasome inhibitor-mediated apoptosis in multidrug-resistant cancer cells.

Multiple drug resistance (MDR) is a major obstacle to attenuating the effectiveness of chemotherapy to many human malignancies. Proteasome inhibition induces apoptosis in a variety of cancer cells and is recognized as a novel anticancer therapy approach. Despite its success, some multiple myeloma patients are resistant or become refractory to ongoing treatment by bortezomib suggesting that chemoresistant cancer cells may have developed a novel mechanism directed against the proteasome inhibitor.

Wnt5A regulates ABCB1 expression in multidrug-resistant cancer cells through activation of the non-canonical PKA/β-catenin pathway.

Multidrug resistance in cancer cells arises from altered drug permeability of the cell. We previously reported activation of the Wnt pathway in ABCB1-overexpressed human uterus sarcoma drug-resistant MES-SA/Dx5 cells through active β-catenin and associated transactivation activities, and upregulation of Wnt-targeting genes. In this study, Wnt5A was found to be significantly upregulated in MES-SA/Dx5 and MCF7/ADR2 cells, suggesting an important role for the Wnt5A signaling pathway in cancer drug resistance.

MicroRNA-5p and -3p co-expression and cross-targeting in colon cancer cells.

Background: Two mature miRNA species may be generated from the 5' and 3' arms of a pre-miRNA precursor. In most cases, only one species remains while the complementary species is degraded. However, co-existence of miRNA-5p and -3p species is increasingly being reported.

Oxidative stress-induced premature senescence in Wharton's jelly-derived mesenchymal stem cells.

Background: On in vitro expansion for therapeutic purposes, the regenerative potentials of mesenchymal stem cells (MSCs) decline and rapidly enter pre-mature senescence probably involving oxidative stress. To develop strategies to prevent or slow down the decline of regenerative potentials in MSC culture, it is important to first address damages caused by oxidative stress-induced premature senescence (OSIPS). However, most existing OSIPS study models involve either long-term culture to achieve growth arrest or immediate growth arrest post oxidative agent treatment and are unsuitable for post-induction studies.

Heterogeneity of osteosarcoma cell lines led to variable responses in reprogramming.

Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells.

Frequent co-expression of miRNA-5p and -3p species and cross-targeting in induced pluripotent stem cells.

Background: A miRNA precursor generally gives rise to one major miRNA species derived from the 5' arm, and are called miRNA-5p. However, more recent studies have shown co-expression of miRNA-5p and -3p, albeit in different concentrations, in cancer cells targeting different sets of transcripts. Co-expression and regulation of the -5p and -3p miRNA species in stem cells, particularly in the reprogramming process, have not been studied.