Epithelial-mesenchymal transition (EMT) has an established role in promoting tumor progression and the acquisition of therapeutic resistance. Here, the EMT phenotype was detected in cisplatin-resistant ovarian cancer tissues and cell lines, and correlated with decreased miR-186 expression, increased Twist1 expression, chemoresistance and poor prognosis in epithelial ovarian cancer (EOC) patients. Introducing miR-186 into EOC cells led to a reduction in twist family bHLH transcription factor 1 (Twist1) expression along with morphological, functional and molecular changes consistent with mesenchymal-to-epithelial transition, G1 cell-cycle arrest and enhanced cell apoptosis, which consequently rendered the cells more sensitive to cisplatin in vitro and in vivo. Furthermore, luciferase reporter and rescue assay results showed that the EMT and drug resistance reversal in response to miR-186 was mediated by Twist1. Collectively, these findings implicate miR-186 as an attractive candidate for overcoming chemoresistance in ovarian cancer therapy.

Mechanical stress plays a critical role in cartilage development and homoeostasis. Chondrocytes are surrounded by a narrow pericellular matrix (PCM), which absorbs dynamic and static forces and transmits them to the chondrocyte surface. Recent studies have demonstrated that molecular components, including perlecan, collagen and hyaluronan, provide distinct physical properties for the PCM and maintain the essential microenvironment of chondrocytes. These physical signals are sensed by receptors and molecules located in the cell membrane, such as Ca2+ channels, the primary cilium and integrins, and a series of downstream molecular pathways are involved in mechanotransduction in cartilage. All mechanoreceptors convert outside signals into chemical and biological signals, which then regulate transcription in chondrocytes in response to mechanical stresses. This review highlights recent progress and focuses on the function of the PCM and cell surface molecules in chondrocyte mechanotransduction. Emerging understanding of the cellular and molecular mechanisms that regulate mechanotransduction will provide new insights into osteoarthritis pathogenesis and precision strategies that could be used in its treatment.

After birth, cardiomyocytes (CM) acquire numerous adaptations in order to efficiently pump blood throughout an animal’s lifespan. How this maturation process is regulated and coordinated is poorly understood. Here, we perform a CRISPR/Cas9 screen in mice and identify serum response factor (SRF) as a key regulator of CM maturation. Mosaic SRF depletion in neonatal CMs disrupts many aspects of their maturation, including sarcomere expansion, mitochondrial biogenesis, transverse-tubule formation, and cellular hypertrophy. Maintenance of maturity in adult CMs is less dependent on SRF. This stage-specific activity is associated with developmentally regulated SRF chromatin occupancy and transcriptional regulation. SRF directly activates genes that regulate sarcomere assembly and mitochondrial dynamics. Perturbation of sarcomere assembly but not mitochondrial dynamics recapitulates SRF knockout phenotypes. SRF overexpression also perturbs CM maturation. Together, these data indicate that carefully balanced SRF activity is essential to promote CM maturation through a hierarchy of cellular processes orchestrated by sarcomere assembly.