Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR-216a.

Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR-216a.
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DOI:
10.1038/s41419-017-0113-5
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发表时间:
2018-01-24
影响因子:
9
通讯作者:
Guo L
Guo L
中科院分区:
生物学1区
文献类型:
--
作者:
Sun Y;Hu B;Wang Q;Ye M;Qiu Q;Zhou Y;Zeng F;Zhang X;Guo Y;Guo L

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尽管小细胞肺癌(SCLC)的治疗取得了进展,但其多药耐药和预后差的问题仍然存在。最近,我们使用微阵列数据,在体外和体内测定,在全球范围内评估了长链非编码RNA(lncRNA)对SCLC化疗耐药性的贡献。我们报道了HOTTIP,编码一种在SCLC中经常扩增的lncRNA,与SCLC细胞的化疗敏感性、增殖和SCLC患者的不良预后相关。此外,机制研究表明,HOTTIP在SCLC进展中作为癌基因发挥作用,通过结合miR-216 a并在这种情况下消除其肿瘤抑制功能。另一方面,HOTTIP通过上调miR-216 a的另一重要靶基因抗凋亡因子BCL-2的表达,共同增强SCLC的化疗耐药性。综上所述,我们的研究确定了HOTTIP在SCLC进展和化疗耐药性中的作用,表明其作为SCLC临床管理的新诊断和预后生物标志物的候选资格。
Despite progress in treatment of small cell lung cancer (SCLC), its multidrug chemoresistance and poor prognosis still remain. Recently, we globally assessed long non-coding RNAs (lncRNAs) for contributions to SCLC chemoresistance using microarray data, in vitro and in vivo assays. Here we reported that HOTTIP, encoding a lncRNA that is frequently amplified in SCLC, was associated with SCLC cell chemosensitivity, proliferation, and poor prognosis of SCLC patients. Moreover, mechanistic investigations showed that HOTTIP functioned as an oncogene in SCLC progression by binding miR-216a and abrogating its tumor-suppressive function in this setting. On the other hand, HOTTIP increased the expression of anti-apoptotic factor BCL-2, another important target gene of miR-216a, and jointly enhanced chemoresistance of SCLC by regulating BCL-2. Taken together, our study established a role for HOTTIP in SCLC progression and chemoresistance suggest its candidacy as a new diagnostic and prognostic biomarker for clinical management of SCLC.
长非编码 RNA HOTTIP 通过调节 HOXA13 促进胰腺癌进展和吉西他滨耐药
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