Medical Oncology

, Volume 29, Issue 1, pp 384–391

miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2

  • Wei Zhu
  • DanXia Zhu
  • Shiqiang Lu
  • Tongshan Wang
  • Jian Wang
  • Binghua Jiang
  • Yongqian Shu
  • Ping Liu
Original Paper

Abstract

MicroRNAs (miRNAs) are short non-coding RNA molecules, which posttranscriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. Here, we investigated the possible role of miRNAs in the development of multidrug resistance (MDR) in human gastric and lung cancer cell lines. We found that miR-497 was downregulated in both multidrug-resistant human gastric cancer cell line SGC7901/vincristine (VCR) and multidrug-resistant human lung cancer cell line A549/cisplatin (CDDP) and the downregulation of miR-497 was concurrent with the upregulation of BCL2 protein, compared with the parental SGC7901 and A549 cell lines, respectively. In vitro drug sensitivity assay demonstrated that overexpression of miR-497 sensitized SGC7901/VCR and A549/CDDP cells to anticancer drugs, respectively. The luciferase activity of BCL2 3′-untranslated region-based reporter constructed in SGC7901/VCR and A549/CDDP cells suggested that BCL2 was the direct target gene of miR-497. Enforced miR-497 expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively. Taken together, our findings first suggested that has-miR-497 could play a role in both gastric and lung cancer cell lines at least in part by modulation of apoptosis via targeting BCL2.

Keywords

MiR-497 Multidrug resistance BCL2 

Abbreviations

miRNAs

MicroRNAs.

MDR

Multidrug resistance.

VCR

Vincristine.

CDDP

Cisplatin

5-Fu

5-fluorouracil

VP-16

Etoposide

ADR

Adriamycin

Supplementary material

12032_2010_9797_MOESM1_ESM.doc (904 kb)
Supplementary material 1 (DOC 903 kb)
12032_2010_9797_MOESM2_ESM.xls (154 kb)
Supplementary material 2 (XLS 154 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Wei Zhu
    • 1
  • DanXia Zhu
    • 3
  • Shiqiang Lu
    • 4
  • Tongshan Wang
    • 1
  • Jian Wang
    • 1
  • Binghua Jiang
    • 2
  • Yongqian Shu
    • 1
    • 2
  • Ping Liu
    • 1
    • 2
  1. 1.Department of OncologyFirst Affiliated Hospital of Nanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.Cancer Center of Nanjing Medical UniversityNanjingPeople’s Republic of China
  3. 3.Department of HaematologyFirst Affiliated Hospital of Nanjing Medical UniversityNanjingPeople’s Republic of China
  4. 4.Department of Microbiology and ImmunologyNanjing Medical UniversityNanjingPeople’s Republic of China

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