MicroRNA miR-21 regulates the metastatic behavior of B16 melanoma cells

Chuan Yang, Junming Yue, Susan R. Pfeffer, Charles R. Handorf, Lawrence Pfeffer

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

MicroRNA-21 (miR-21) is overexpressed in many human tumors and has been linked to various cellular processes altered in cancer. miR-21 is also up-regulated by a number of inflammatory agents, including IFN, which is of particular interest considering the close relationship between inflammation and cancer. Because miR-21 appears to be overexpressed in human melanoma, we examined the role of miR-21 in cancer development and metastasis in B16 mouse melanoma cells. We found that miR-21 is a member of an IFN-induced miRNA subset that requires STAT3 activation. To characterize the role of miR-21 in melanoma behavior, we transduced B16 cells with lentivirus encoding a miR-21 antagomir and isolated miR-21 knockdown B16 cells. miR-21 knockdown or IFN treatment alone inhibited B16 cell proliferation and migration in vitro, and in combination they had an enhanced effect. Moreover, miR-21 knockdown sensitized B16 cells to IFN-induced apoptosis. In B16 cells miR-21 targeted tumor suppressor (PTEN and PDCD4) and antiproliferative (BTG2) proteins. To characterize the role of miR-21 in vivo, empty vector- and antagomiR-21-transduced B16 melanoma cells were injected via tail vein into syngeneic C57BL/6 mice. Although empty vector-transduced B16 cells produced large lung metastases, miR-21 knockdown cells only formed small lung lesions. Importantly, miR-21 knockdown tumor-bearing mice exhibited prolonged survival compared with empty vector tumor-bearing mice. Thus, miR-21 regulates the metastatic behavior of B16 melanoma cells by promoting cell proliferation, survival, and migration/invasion as well as by suppressing IFN action, providing important new insights into the role of miR-21 in melanoma.

Original languageEnglish (US)
Pages (from-to)39172-39178
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number45
DOIs
StatePublished - Nov 11 2011

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Experimental Melanomas
MicroRNAs
Tumors
Bearings (structural)
Neoplasms
Melanoma
Cell proliferation
Cell Movement
Cell Proliferation
Neoplasm Metastasis
Lung
Lentivirus

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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MicroRNA miR-21 regulates the metastatic behavior of B16 melanoma cells. / Yang, Chuan; Yue, Junming; Pfeffer, Susan R.; Handorf, Charles R.; Pfeffer, Lawrence.

In: Journal of Biological Chemistry, Vol. 286, No. 45, 11.11.2011, p. 39172-39178.

Research output: Contribution to journalArticle

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