Random small interfering RNA library screen identifies siRNAs that induce human erythroleukemia cell differentiation

Abstract

Cancers are characterized by poor differentiation. Differentiation therapy is a strategy to alleviate malignant phenotypes by inducing cancer cell differentiation. Here we carried out a combinatorial high-throughput screen with a random siRNA library on human erythroleukemia K-562 cell differentiation. Two siRNAs screened from the library were validated to be able to induce erythroid differentiation to varying degrees, determined by CD235 and globin up-regulation, GATA-2 down-regulation, and cell growth inhibition. The screen we performed here is the first trial of screening cancer differentiation-inducing agents from a random siRNA library, demonstrating that a random siRNA library can be considered as a new resource in efforts to seek new therapeutic agents for cancers. As a random siRNA library has a broad coverage for the entire genome, including known/unknown genes and protein coding/non-coding sequences, screening using a random siRNA library can be expected to greatly augment the repertoire of therapeutic siRNAs for cancers.

Keywords:

• siRNA library
• leukemia
• differentiation

Acknowledgements

Microarray experiments were performed by KangChen Bio-tech, Shanghai, China.

Declaration of interest: This work was supported by Grant 2006AA02Z118 from the National High Technology Research and Development Program of China (863 Program), Grant 2007CB946901 from the Major State Basic Research Development Program of China (973 Program), and a grant from the Program for New Century Excellent Talents in the University of China.