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.
细胞外基质（ECM）对癌症进展和化疗敏感性至关重要。卵巢癌死亡率高、预后差，严重威胁着女性生命健康。但目前ECM硬度对卵巢癌长链非编码RNA(lncRNAs)表达谱和化疗抗性的调控作用尚不清楚。因此，本研究通过分析不同基质硬度卵巢癌细胞转录组数据，发现基质硬化导致大量lncRNAs表达上调，但SNHG8表达显著下调，并利用聚二甲基硅氧烷（PDMS）水凝胶培养的卵巢癌细胞进行验证。研究发现敲低SNHG8降低了同源重组修复效率以及卵巢癌细胞对依托泊苷和顺铂的敏感性。GEPIA数据分析显示，SNHG8在卵巢癌组织中显著下调，其表达水平与卵巢癌患者预后呈负相关。本研究显示基质硬化相关lncRNA SNHG8与卵巢癌化疗敏感性和预后密切相关，可望作为指导卵巢癌化疗用药和预测预后的分子标志物。.
Keywords: Chemosensitivity; Long non-coding RNA; Matrix stiffness; Ovarian cancer; SNHG8.