Memory-promoting function of miR-379-5p attenuates CD8 T cell exhaustion by targeting immune checkpoints.

Background: MicroRNAs (miRNAs) are epigenetic regulators of T cell maturation and exhaustion. However, the mechanisms by which miRNAs influence T cell function in tumor environments remain unclear. This study focuses on miR-379-5p, which counteracts T cell exhaustion and enhances antitumor responses.

Loss of tyrosine 211 phosphorylation of proliferating cell nuclear antigen (PCNA) enhances postnatal mammary gland development.

The intricately orchestrated progression of mammary tissue development involves the precise coordination of gland differentiation and cellular proliferation. Nevertheless, the understanding of the role and regulatory mechanisms governing the DNA replication machinery in mammary gland development remains limited. Given the essential role of DNA replication in the viability of living cells, any genetic disturbance to its replicative function, in any form, will impede organ development.

The Functions of PCNA in Tumor Stemness and Invasion.

Invasion is the most prominent lethal feature of malignant cancer. However, how cell proliferation, another important feature of tumor development, is integrated with tumor invasion and the subsequent cell dissemination from primary tumors is not well understood. Proliferating cell nuclear antigen (PCNA) is essential for DNA replication in cancer cells.

miR-4759 suppresses breast cancer through immune checkpoint blockade.

Programmed cell death protein 1 (PD-1)/ programmed cell death protein ligand 1 (PD-L1) is the key immune checkpoint governing evasion of advanced cancer from immune surveillance. Immuno-oncology (IO) therapy targeting PD-1/PD-L1 with traditional antibodies is a promising approach to multiple cancer types but to which the response rate remains moderate in breast cancer, calling for the need of exploring alternative IO targeting approaches. A miRNA-gene network was integrated by a bioinformatics approach and corroborated with The Cancer Genome Atlas (TCGA) to screen miRNAs regulating immune checkpoint genes and associated with patient survival.

Suppression of breast cancer cells resistant to a pure anti-estrogen with CAR-transduced natural killer cells.

Anti-estrogens as hormone therapy are the mainstay treatment for estrogen receptor (ER)-positive breast cancer. ER inhibitors through modulating the transcriptional function of ER have been the frontline anti-estrogens to which refractory phenotype often developed in advanced cancer. The anti-estrogen fulvestrant is currently the only clinically approved pure anti-estrogen which causes ER degradation.

Evading immune surveillance via tyrosine phosphorylation of nuclear PCNA.

Increased DNA replication and metastasis are hallmarks of cancer progression, while deregulated proliferation often triggers sustained replication stresses in cancer cells. How cancer cells overcome the growth stress and proceed to metastasis remains largely elusive. Proliferating cell nuclear antigen (PCNA) is an indispensable component of the DNA replication machinery.

Imatinib (STI571) Inhibits the Expression of Angiotensin-Converting Enzyme 2 and Cell Entry of the SARS-CoV-2-Derived Pseudotyped Viral Particles.

A group of clinically approved cancer therapeutic tyrosine kinase inhibitors was screened to test their effects on the expression of angiotensin-converting enzyme 2 (ACE2), the cell surface receptor for SARS-CoV-2. Here, we show that the receptor tyrosine kinase inhibitor imatinib (also known as STI571, Gleevec) can inhibit the expression of the endogenous ACE2 gene at both the transcript and protein levels. Treatment with imatinib resulted in inhibition of cell entry of the viral pseudoparticles (Vpps) in cell culture.

Long non-coding RNA HOTAIR in circulatory exosomes is correlated with ErbB2/HER2 positivity in breast cancer.

Cancer cells are known to produce and secret extracellular vesicles for intercellular communication through the carried cargos. HOTAIR (HOX transcript antisense intergenic RNA), a well-studied long non-coding RNA (lncRNA), plays a critical role in cancer progression. In several cancer types it has been shown that HOTAIR-containing exosomes are produced by cancer cells.

The exosomal compartment protects epidermal growth factor receptor from small molecule inhibitors.

Epidermal growth factor receptor (EGFR) plays a significant role in promoting breast cancer progression. However, targeting EGFR as a single treatment only resulted in moderate efficacy to the disease. The underlying mechanism of low responsiveness to EGFR inhibition remains largely unclear.

Arecoline N-oxide regulates oral squamous cell carcinoma development through NOTCH1 and FAT1 expressions.

Areca nut has been evaluated as a group I carcinogen to humans. However, the exact compounds of areca nut causing oral cancer remain unproven. Previous findings from our lab revealed that arecoline N-oxide (ANO), a metabolite of arecoline, exhibits an oral fibrotic effect in immune-deficient NOD/SCID mice.

Arecoline N-Oxide Upregulates Caspase-8 Expression in Oral Hyperplastic Lesions of Mice.

Areca nut is strongly associated with oral squamous cell carcinoma (OSCC) occurrence. Arecoline N-oxide (ANO), a metabolite of the areca alkaloid arecoline, exhibits an oral fibrotic effect in NOD/SCID mice. Caspase-8, a cysteine protease encoded by the CASP8 gene, is a central mediator in the extrinsic apoptotic pathway via death receptors.

Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development.

A number of genetic variants have been associated with cancer occurrence, however it may be the acquired somatic mutations (SMs) that drive cancer development. This study investigates the potential SMs and related genetic variants associated with the occurrence and development of head and neck squamous cell carcinoma (HNSCC). We identified several SMs in NOTCH1 from whole-exome sequencing and validated them in a 13-year cohort of 128 HNSCC patients using a high-resolution melting analysis and resequencing.