[Matrix stiffening related lncRNA SNHG8 regulates chemosensitivity of ovarian cancer].

Extracellular matrix (ECM) has been implicated in tumor progress and chemosensitivity. Ovarian cancer brings a great threat to the health of women with a significant feature of high mortality and poor prognosis. However, the potential significance of matrix stiffness in the pattern of long non-coding RNAs (lncRNAs) expression and ovarian cancer drug sensitivity is still largely unkown. Here, based on RNA-seq data of ovarian cancer cell cultured on substrates with different stiffness, we found that a great amount of lncRNAs were upregulated in stiff group, whereas SNHG8 was significantly downregulated, which was further verified in ovarian cancer cells cultured on polydimethylsiloxane (PDMS) hydrogel. Knockdown of SNHG8 led to an impaired efficiency of homologous repair, and decreased cellular sensitivity to both etoposide and cisplatin. Meanwhile, the results of the GEPIA analysis indicated that the expression of SNHG8 was significantly decreased in ovarian cancer tissues, which was negatively correlated with the overall survival of patients with ovarian cancer. In conclusion, matrix stiffening related lncRNA SNHG8 is closely related to chemosensitivity and prognosis of ovarian cancer, which might be a novel molecular marker for chemotherapy drug instruction and prognosis prediction.

Stiff substrates enhance cultured neuronal network activity.

The mechanical property of extracellular matrix and cell-supporting substrates is known to modulate neuronal growth, differentiation, extension and branching. Here we show that substrate stiffness is an important microenvironmental cue, to which mouse hippocampal neurons respond and integrate into synapse formation and transmission in cultured neuronal network. Hippocampal neurons were cultured on polydimethylsiloxane substrates fabricated to have similar surface properties but a 10-fold difference in Young's modulus. Voltage-gated Ca(2+) channel currents determined by patch-clamp recording were greater in neurons on stiff substrates than on soft substrates. Ca(2+) oscillations in cultured neuronal network monitored using time-lapse single cell imaging increased in both amplitude and frequency among neurons on stiff substrates. Consistently, synaptic connectivity recorded by paired recording was enhanced between neurons on stiff substrates. Furthermore, spontaneous excitatory postsynaptic activity became greater and more frequent in neurons on stiff substrates. Evoked excitatory transmitter release and excitatory postsynaptic currents also were heightened at synapses between neurons on stiff substrates. Taken together, our results provide compelling evidence to show that substrate stiffness is an important biophysical factor modulating synapse connectivity and transmission in cultured hippocampal neuronal network. Such information is useful in designing instructive scaffolds or supporting substrates for neural tissue engineering.

An experimental study on collagen content and biomechanical properties of sclera after posterior sclera reinforcement.

BACKGROUND: The development of pathological myopia is associated with reduced scleral collagen accumulation, scleral thinning, and loss of scleral tissue, in both humans and animal models. Posterior scleral reinforcement (PSR) was considered as an effective way for treating pathological myopia. Yet it is not well understood the possible role of collagen on the sclera reinforcement mechanisms in the PSR surgery. METHODS: PSR surgery was performed on the normal adult New Zealand white rabbits eyes. Human sclera was used as reinforcement materials. At 1, 2, 3, 6, 9 months after the PSR surgery, scleral hydroxyproline (Hyp) synthesis and collagen fibers arrangement were determined by enzymolysic hydrolysis assay and histological morphology technique. An Instron test machine was used to investigate the elastic modulus of sclera. FINDINGS: It was found that the elastic modulus and Hyp content of reinforced sclera were lower at first month after surgery, and then gradually up to physiological level in the following months. Those two indexes were close to that of the normal control groups at 9 months. INTERPRETATION: These findings indicate that sclera elastic modulus was associated with both change of Hyp content and collagen fibers arrangement after PSR. The therapeutic effect of PSR surgery was confirmed not only from biological but also biomechanical aspects.