Biology subjects

Chou, H.-C.

Publications and source records attributed to Chou, H.-C..

4 recordsLinked to original sources

bioRxiv2026

Norepinephrine Induces Proliferation and Migration of Human Pulmonary Artery Smooth Muscle Cells via Endothelin 1

Background: Pulmonary arterial hypertension (PAH) is a serious disease with poor prognosis, especially in infants or preterm babies and there is still no optimal treatment for this disease. Noradrenalin (NE) is a vasoactive mediator which is released by sympathetic ganglion. According to previous studies, NE/1-adrenoreceptors is not only in regulating normal physiologic responses, but also in the pathogenesis of PAH. However, the mechanisms of NE in PAH are not fully understood. Methods: Human PASMC (PASMC) was used in this study. Cell viability assay and Wound healing assay were used to evaluate the proliferation and migration of PASMC. Immunoprecipitation and western blots analysis were used to investigate the mechanisms which involved in NE-induced PASMC proliferation. Results: We investigated that NE could induce human PASMC proliferation and migration. Furthermore, we first find that endothelin 1 (ET-1) signaling pathway plays an important role in NE-induced PASMC proliferation. ET1 is a critical molecular which is known for regulating cell growth and migration. We investigated that NE could increase NE-1 secretion, further enhancing ET-1 bind to its receptors. For further clarifying the downstream signals in NE/ET-1 induced PASMC proliferation, we detected the phosphorylation and expression levels of ERK and JNK. Conclusions: By combining the results from ours and previous studies, we believed that JNK/c-jun pathway may play an important role in NE-induced PASMC proliferation. Key Words: Noradrenaline; Pulmonary Arterial Hypertension; Pulmonary Artery Smooth Muscle Cells; Endothelin-1; JNK/c-Jun Signaling.

molecular biology↗

bioRxiv2025

RUNX2 inhibition disrupts a PAX3::FOXO1-RUNX2 feed-forward loop and dismantles oncogenic gene programs in fusion-positive rhabdomyosarcoma

Fusion-positive rhabdomyosarcoma is an aggressive pediatric cancer of skeletal muscle lineage, with a 5-year overall survival of <30% for high-risk disease, and <8% when metastatic. The PAX3::FOXO1 fusion gene, resulting from t(2:13), is a signature driver of fusion-positive rhabdomyosarcoma, but similar to other transcription-factor based fusion genes in other cancers, not currently pharmacologically tractable. To identify novel druggable proteins in fusion-positive rhabdomyosarcoma tumor tissue and cell lines, we performed mRNA-seq of RMS patient tumors and utilizing the human FP-RMS cell lines Rh30 and Rh4, found that the RUNX2 transcription factor was the top druggable dependency. In vitro loss of function studies using genetic (RNAi) or pharmacologic (small molecule CADD522) inhibition showed that RUNX2 suppression inhibited FP-RMS cell growth, induced myogenic differentiation and apoptosis, and phenocopied PAX3::FOXO1 suppression. In vivo loss of function studies using conditional (dox-inducible) or pharmacologic (small molecule CADD522) blockade of tumor growth in a xenograft model system showed that RUNX2 suppression inhibited tumor growth. Mechanistically, we identify a PAX3::FOXO1 feed-forward loop whereby PAX3::FOXO1 binds a RUNX2 enhancer to upregulate gene expression alongside MYOD1, while RUNX2 expression supports the expression of PAX3::FOXO1 at the mRNA and protein level. SignificanceRUNX2 inhibition reduces PAX3::FOXO1 expression and signaling, which impairs fusion-positive rhabdomyosarcoma oncogenic phenotypes. In vivo treatment with CADD522 decreased tumor growth and increased survival, indicating that RUNX2 is a promising therapeutic target.

cancer biology↗

bioRxiv2023

Quantitative Analysis of Macrophage Uptake and Retention of Fluorescent Organosilica Nanoparticles

This study investigates the uptake and retention of stable fluorescent organosilica nanoparticles by macrophages, which play a vital role in scavenging environmental nanoparticles and nanomedicine within the body. We used rhodamine 6G-loaded fluorescent organosilica nanoparticles (SiNP-R6G) synthesized from a thiol-functionalized organosilane precursor. Our primary objective was to establish a quantitative relationship between fluorescent measurements and nanoparticle tracking analysis, enabling the precise "counting" of nanoparticles taken up by macrophages under kinetic measurement conditions. Our kinetic study demonstrated a concentration-dependent, saturable internalization of nanoparticles in a model macrophage (RAW 264.7 cells), with a maximum uptake rate (Vmax) of 7.9 x 104 nanoparticles per hour per cell. The estimated number concentration of nanoparticles for half-maximum uptake was approximately 0.8 trillion nanoparticles per milliliter, and a significant portion ([~]80%) of internalized SiNP-R6G remained entrapped within the cells for 48 hours, indicating the sustained particle retention capacity of macrophages. These findings highlight the successful development of a methodology to accurately "count" the cellular uptake of nanoparticles in macrophages, providing valuable insights into the kinetics and retention capabilities of macrophages for nanoparticles.

pharmacology and toxicology↗

bioRxiv2020

The human Origin Recognition Complex is essential for pre-RC assembly, mitosis and maintenance of nuclear structure.

The Origin Recognition Complex (ORC) cooperates with CDC6, MCM2-7, and CDT1 to form pre- RC complexes at origins of DNA replication. Here we report tiling-sgRNA CRISPR screens that show that each subunit of ORC and CDC6 are essential in human cells. Using an auxin-inducible degradation system, stable cell lines were created that ablate ORC2 rapidly, revealing multiple cell division cycle phenotypes. The primary defect in the absence of ORC2 was cells encountering difficulty in initiating DNA replication or progressing through the cell division cycle due to reduced MCM2-7 loading onto chromatin in G1 phase. The nuclei of ORC2 deficient cells were also large, with decompacted heterochromatin. Some ORC2 deficient cells that completed DNA replication entered into, but never exited mitosis. ORC1 knockout cells also demonstrated extremely slow cell proliferation and abnormal cell and nuclear morphology. Thus, ORC proteins and CDC6 are indispensable for normal cellular proliferation and contribute to nuclear organization.

molecular biology↗