长链非编码 RNA XIST 的上调通过反向下调 hsa-miR-214-3p 对上皮性卵巢癌细胞发挥抗癌作用。
Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p.
机构信息
Department of Chinese Medicine, China-Japan Union Hospital of Jilin University, Changchun, China.
Department of Pharmacy, China-Japan Union Hospital of Jilin University, Changchun, China.
出版信息
J Gynecol Oncol. 2018 Nov;29(6):e99. doi: 10.3802/jgo.2018.29.e99.
OBJECTIVE
The present study is to evaluate the biological functions of long non-coding RNA (lncRNA), X-inactive specific transcript, X-inactive specific transcript (XIST) in human epithelial ovarian cancer (EOC).
METHODS
XIST was upregulated in EOC cell lines, CAOV3 and OVCAR3 cells by lentiviral transduction. The effects of XIST overexpression on cancer cell proliferation, invasion, chemosensitivity and in vivo tumor growth were investigated, respectively. Possible sponging interaction between XIST and human microRNA hsa-miR-214-3p was further evaluated. Furthermore, hsa-miR-214-3p was overexpressed in XIST-upregulated CAOV3 and OVCAR3 cells to evaluate its effect on XIST-mediated EOC regulation.
RESULTS
Lentivirus-mediated XIST upregulation had significant anticancer effects in CAOV3 and OVCAR3 cells by suppressing cancer cell proliferation, invasion, increasing cisplatin chemosensitivity and inhibiting in vivo tumor growth. Hsa-miR-214-3p was confirmed to directly bind XIST, and inversely downregulated in XIST-upregulated EOC cells. In EOC cells with XIST upregulation, secondary lentiviral transduction successfully upregulated hsa-miR-214-3p expression. Subsequently, hsa-miR-214-3p upregulation functionally reversed the anticancer effects of XIST-upregulation in EOC.
CONCLUSION
Upregulation of lncRNA XIST may suppress EOC development, possibly through sponging effect to induce hsa-miR-214-3p downregulation.
目的
本研究旨在评估长链非编码 RNA（lncRNA）X 失活特异性转录物（XIST）在人卵巢上皮性癌（EOC）中的生物学功能。
方法
通过慢病毒转导使 EOC 细胞系 CAOV3 和 OVCAR3 细胞中 XIST 上调。分别研究了 XIST 过表达对癌细胞增殖、侵袭、化疗敏感性和体内肿瘤生长的影响。进一步评估了 XIST 和人微小 RNA hsa-miR-214-3p 之间可能的海绵吸附相互作用。此外，在 XIST 上调的 CAOV3 和 OVCAR3 细胞中过表达 hsa-miR-214-3p，以评估其对 XIST 介导的 EOC 调节的影响。
结果
慢病毒介导的 XIST 上调通过抑制癌细胞增殖、侵袭、增加顺铂化疗敏感性和抑制体内肿瘤生长，对 CAOV3 和 OVCAR3 细胞具有显著的抗癌作用。hsa-miR-214-3p 被证实可直接结合 XIST，并在 XIST 上调的 EOC 细胞中呈反式下调。在 XIST 上调的 EOC 细胞中，二次慢病毒转导成功上调了 hsa-miR-214-3p 的表达。随后，hsa-miR-214-3p 的上调功能逆转了 XIST 上调对 EOC 的抗癌作用。
结论
lncRNA XIST 的上调可能抑制 EOC 的发展，可能通过海绵吸附作用诱导 hsa-miR-214-3p 下调。
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