Discovery of novel cell proliferation-enhancing gene by random siRNA library based combinatorial screening

Xiahui Xiong, Yabin Lu, Lishu Zhang, Bo Wang, Yingtao Zhao, Xiu-Jie Wang, Xiaofang Huo, Yan Shen, Zicai Liang, Meihong Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Bone remodeling is tightly controlled by the actions of osteoblast and osteoclast. Impaired osteoblast proliferation and differentiation may disrupt the balance and lead to pathological symptom such as osteoporosis. To help understand the molecular mechanism of osteoblast proliferation, we performed a phenotype-driven high throughput screening with a random siRNA library, in search of novel genes that can accelerate murine preosteoblast MC3T3-E1 cell proliferation. Three siRNAs screened from the library were able to enhance MC3T3-E1 cell proliferation significantly. One of the proliferation-enhancing siRNAs (B7) was further subjected to expression profiling to pinpoint genes that putatively act down stream of it. A number of genes were regulated in response to proliferation-enhancing siRNA B7. Among these genes, Tmed2, which has never been reported yet in cell proliferation, was verified to be able to enhance MC3T3-E1 cell proliferation when over-expressed. Our screening process with random siRNA library provided an alternative strategy in addition to gene-specific siRNA library, in search of novel functional genes in genome scale.

Original languageEnglish (US)
Pages (from-to)798-806
Number of pages9
JournalCombinatorial Chemistry and High Throughput Screening
Volume13
Issue number9
DOIs
StatePublished - Nov 2010
Externally publishedYes

Keywords

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Combinatorial Chemistry Techniques
  • Gene Library
  • Mice
  • RNA, Small Interfering/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • Vesicular Transport Proteins/genetics
  • Cell proliferation
  • Functional screening
  • Tmed2
  • SiRNA library
  • Osteoblast
  • Random library

ASJC Scopus subject areas

  • Drug Discovery
  • Computer Science Applications
  • Organic Chemistry

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