Lin28-let7 调节 K-Ras 激活的人癌细胞的放射敏感性。

Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras.

机构信息

Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnamsi, Korea.

出版信息

Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):5-8. doi: 10.1016/j.ijrobp.2009.08.028.

DOI:10.1016/j.ijrobp.2009.08.028

PMID:20005451

Abstract

PURPOSE

To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling.

METHODS AND MATERIALS

A549 lung carcinoma cells and ASPC1 pancreatic cancer cells possessing K-RAS mutation were transfected with pre-let7a microRNA or Lin28 siRNA, respectively. Clonogenic assay, quantitative reverse transcription polymerase chain reaction, and Western analysis were performed. The effects of Lin28 on SQ20B cells having wild-type K-RAS, and a normal fibroblast were also assessed.

RESULTS

The overexpression of let-7a decreased expression of K-Ras and radiosensitized A549 cells. Inhibition of Lin28, a repressor of let-7, attenuated K-Ras expression and radiosensitized A549 and ASPC1 cells. Neither SQ20B cells expressing wild-type K-RAS nor HDF, the normal human fibroblasts, were radiosensitized by this approach.

CONCLUSIONS

The Lin28-let7 regulatory network may be a potentially useful therapeutic target for overcoming the radioresistance of human cancers having activated K-Ras signaling.

摘要

目的

评估针对 Lin28-let7 微 RNA 调控网络的潜在作用，以克服激活 K-Ras 信号的癌细胞的放射抵抗性。

方法与材料

用 pre-let7a 微 RNA 或 Lin28 siRNA 分别转染具有 K-RAS 突变的 A549 肺癌细胞和 ASPC1 胰腺癌细胞。进行集落形成实验、定量逆转录聚合酶链反应和 Western 分析。还评估了 Lin28 对具有野生型 K-RAS 的 SQ20B 细胞和正常成纤维细胞的影响。

结果

let-7a 的过表达降低了 K-Ras 的表达并使 A549 细胞对放射敏感。Lin28 的抑制，let-7 的抑制剂，减弱了 K-Ras 的表达并使 A549 和 ASPC1 细胞对放射敏感。表达野生型 K-RAS 的 SQ20B 细胞和正常的人成纤维细胞（HDF）均未通过这种方法产生放射敏感性。