Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, PR China.
Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, PR China.
Biochem Biophys Res Commun. 2018 Jul 2;501(4):1034-1040. doi: 10.1016/j.bbrc.2018.05.104. Epub 2018 May 19.
Increasing evidence has demonstrated the involvement of dysregulated long non-coding RNAs (lncRNAs) in chemoresistance acting as potential oncogenes or tumor suppressors in various cancers. Nevertheless, the profound molecular mechanisms of lncRNAs in ovarian cancer (OC) chemoresistance is not well elucidated. The objective of this work was to investigate the role and molecular mechanisms of urothelial carcinoma associated 1 (UCA1) in paclitaxel (PTX) resistance in OC. Our results indicated that UCA1 was significantly up-regulated in PTX-resistant OC cells (SKOV3/PTX and HeyA-8/PTX) compared with their parental cells (SKOV3 and HeyA-8). Functionally, UCA1 knockdown sensitized SKOV3/PTX and HeyA-8/PTX cells to PTX through enhancing PTX-induced apoptosis. Mechanistically, UCA1 silencing induced PTX sensitivity of SKOV3/PTX and HeyA-8/PTX cells by de-repressing ABCB1 through sponging miR-129. Collectively, our study elaborated a novel UCA1/miR-129/ABCB1 regulatory axis underlying PTX resistance of OC cells, providing a potential therapeutic target for OC.
越来越多的证据表明，失调的长非编码 RNA（lncRNA）参与了多种癌症的化疗耐药，作为潜在的癌基因或肿瘤抑制因子发挥作用。然而，lncRNA 在卵巢癌（OC）化疗耐药中的深刻分子机制尚不清楚。本研究旨在探讨尿路上皮癌相关 1（UCA1）在 OC 紫杉醇（PTX）耐药中的作用及其分子机制。我们的结果表明，与亲本细胞（SKOV3 和 HeyA-8）相比，PTX 耐药 OC 细胞（SKOV3/PTX 和 HeyA-8/PTX）中 UCA1 明显上调。功能上，UCA1 敲低通过增强 PTX 诱导的细胞凋亡使 SKOV3/PTX 和 HeyA-8/PTX 细胞对 PTX 敏感。在机制上，UCA1 沉默通过海绵吸附 miR-129 来解除 ABCB1 的抑制作用，从而诱导 SKOV3/PTX 和 HeyA-8/PTX 细胞对 PTX 敏感。总之，我们的研究阐述了一个新的 UCA1/miR-129/ABCB1 调节轴，该轴是 OC 细胞对 PTX 耐药的基础，为 OC 提供了一个潜在的治疗靶点。
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