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MIR600HG 通过靶向结直肠癌细胞中的 ALDH1A3 抑制转移并增强奥沙利铂化疗敏感性。

MIR600HG suppresses metastasis and enhances oxaliplatin chemosensitivity by targeting ALDH1A3 in colorectal cancer.

机构信息

Department of Gastroenterology, Eighth Medical Center of PLA General Hospital, Beijing 100853, China.

Medical School of Chinese PLA, Department of Gastroenterology, Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20200390.

Abstract

BACKGROUND

Metastasis and chemoresistance indicate a poor prognosis in colorectal cancer (CRC) patients. However, the mechanisms that lead to the development of chemoresistance and metastasis in CRC remain unclear.

MATERIALS AND METHODS

We combined clinical and experimental studies to determine the role of MIR600HG in CRC metastasis and chemoresistance. The statistical analysis was performed using GraphPad Prism software, version 8.0.

RESULTS

We detected down-regulated expression of long non-coding RNA (lncRNA) MIR600HG in CRC specimens and cell lines compared with normal controls, and the expression level of MIR600HG was inversely correlated with the overall survival of CRC patients. The inhibition of MIR600HG stimulated CRC cell metastasis and chemoresistance. In addition, our data showed that the inhibition of MIR600HG stimulated CRC stemness, while the overexpression of MIR600HG suppressed stemness. Importantly, our animal experiments showed that MIR600HG inhibited tumour formation and that the combination of MIR600HG inhibition and oxaliplatin (Oxa) treatment significantly inhibited tumour growth compared with that with either intervention alone. Furthermore, we demonstrated that MIR600HG exerts its anticancer role by targeting ALDH1A3 in CRC.

CONCLUSIONS

Our data suggest that MIR600HG functions as a tumour suppressor and that the overexpression of MIR600HG inhibits tumour invasion and enhances chemosensitivity, providing a new strategy for CRC treatment.

摘要

背景

转移和化疗耐药性表明结直肠癌(CRC)患者预后不良。然而,导致 CRC 发生化疗耐药性和转移的机制尚不清楚。

材料与方法

我们结合临床和实验研究来确定 MIR600HG 在 CRC 转移和化疗耐药性中的作用。统计分析使用 GraphPad Prism 软件,版本 8.0 进行。

结果

与正常对照相比,我们在 CRC 标本和细胞系中检测到长非编码 RNA(lncRNA)MIR600HG 的表达下调,并且 MIR600HG 的表达水平与 CRC 患者的总生存期呈负相关。MIR600HG 的抑制刺激了 CRC 细胞的转移和化疗耐药性。此外,我们的数据表明,MIR600HG 的抑制刺激了 CRC 干性,而 MIR600HG 的过表达则抑制了干性。重要的是,我们的动物实验表明 MIR600HG 抑制了肿瘤的形成,并且 MIR600HG 抑制与奥沙利铂(Oxa)治疗的联合应用与单独干预相比显著抑制了肿瘤的生长。此外,我们证明 MIR600HG 通过靶向 CRC 中的 ALDH1A3 发挥其抗癌作用。

结论

我们的数据表明,MIR600HG 作为肿瘤抑制因子发挥作用,MIR600HG 的过表达抑制肿瘤侵袭并增强化疗敏感性,为 CRC 的治疗提供了新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/7189477/b0ebfbbbcc24/bsr-40-bsr20200390-g1.jpg

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