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[基质硬化相关长链非编码RNA SNHG8调控卵巢癌的化疗敏感性]

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

作者信息

Cheng Zina, Ma Xiaolu, Zhang Quanyou, Chen Weiyi

机构信息

College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, P. R. China.

Institute of Zoology, University of Chinese Academy of Sciences, Beijing 100101, P. R. China.

出版信息

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2023 Feb 25;40(1):87-94. doi: 10.7507/1001-5515.202205038.

Abstract

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.

摘要

细胞外基质(ECM)与肿瘤进展和化疗敏感性有关。卵巢癌对女性健康构成巨大威胁,具有高死亡率和预后差的显著特征。然而,基质硬度在长链非编码RNA(lncRNAs)表达模式和卵巢癌药物敏感性方面的潜在意义仍 largely unkown。在此,基于在不同硬度底物上培养的卵巢癌细胞的RNA-seq数据,我们发现硬基质组中有大量lncRNAs上调,而SNHG8显著下调,这在聚二甲基硅氧烷(PDMS)水凝胶上培养的卵巢癌细胞中得到进一步验证。敲低SNHG8导致同源修复效率受损,并降低细胞对依托泊苷和顺铂的敏感性。同时,GEPIA分析结果表明,SNHG8在卵巢癌组织中的表达显著降低,这与卵巢癌患者的总生存期呈负相关。总之,与基质硬化相关的lncRNA SNHG8与卵巢癌的化疗敏感性和预后密切相关,可能是化疗药物指导和预后预测的新型分子标志物。

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