Matrix stiffness-sensitive long-non coding RNA NEAT1 seeded paraspeckles in cancer cells

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Abstract

Cancer progression is influenced by changes in the tumour microenvironment, such as the stiffening of the extracellular matrix. Yet our understanding of how cancer cells sense and convert mechanical stimuli into biochemical signals and physiological responses is still limited. The long non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), which forms the backbone of subnuclear 'paraspeckle' bodies, has been identified as a key genetic regulator in numerous cancers. Here, we investigated whether paraspeckles, as defined by NEAT1 localisation, are mechanosensitive. Using tuneable polyacrylamide hydrogels of extreme stiffnesses, we measured paraspeckle parameters in several cancer cell lines and observed an increase in paraspeckles in cells cultured on soft (3 kPa) hydrogels compared to stiffer (40 kPa) hydrogels. This response to soft substrate is erased when cells are first conditioned on stiff substrate, then transferred onto soft hydrogels, suggestive of mechanomemory upstream of paraspeckle regulation. We also examined some well-characterized mechanosensitive markers, but found that Lamin A expression, as well as YAP and MRTF-A nuclear translocation did not show consistent trends between stiffnesses, despite all cell types having increased migration, nuclear and cell area on stiffer hydrogels. We thus propose that paraspeckles may prove of use as mechanosensors in cancer mechanobiology.

Original languageEnglish
Pages (from-to)1654-1662
Number of pages9
JournalMolecular Biology of the Cell
Volume31
Issue number16
DOIs
Publication statusPublished - 21 Jul 2020

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