miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers

Liqin Du, Maria C. Subauste, Christopher DeSevo, Zhenze Zhao, Michael Baker, Robert Borkowski, Jeoffrey J. Schageman, Rachel Greer, Chin Rang Yang, Milind Suraokar, Ignacio I. Wistuba, Adi F. Gazdar, John D. Minna, Alexander Pertsemlidis

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

NSCLC (non-small cell lung cancer) often exhibits resistance to paclitaxel treatment. Identifying the elements regulating paclitaxel response will advance efforts to overcome such resistance in NSCLC therapy. Using in vitro approaches, we demonstrated that over-expression of the microRNA miR-337-3p sensitizes NCI-H1155 cells to paclitaxel, and that miR-337-3p mimic has a general effect on paclitaxel response in NSCLC cell lines, which may provide a novel adjuvant strategy to paclitaxel in the treatment of lung cancer. By combining in vitro and in silico approaches, we identified STAT3 and RAP1A as direct targets that mediate the effect of miR-337-3p on paclitaxel sensitivity. Further investigation showed that miR-337-3p mimic also sensitizes cells to docetaxel, another member of the taxane family, and that STAT3 levels are significantly correlated with taxane resistance in lung cancer cell lines, suggesting that endogenous STAT3 expression is a determinant of intrinsic taxane resistance in lung cancer. The identification of a miR-337-3p as a modulator of cellular response to taxanes, and STAT3 and RAP1A as regulatory targets which mediate that response, defines a novel regulatory pathway modulating paclitaxel sensitivity in lung cancer cells, which may provide novel adjuvant strategies along with paclitaxel in the treatment of lung cancer and may also provide biomarkers for predicting paclitaxel response in NSCLC.

Original languageEnglish (US)
Article numbere39167
JournalPLoS One
Volume7
Issue number6
DOIs
StatePublished - Jun 18 2012

Fingerprint

taxanes
paclitaxel
lung neoplasms
Paclitaxel
Non-Small Cell Lung Carcinoma
Cells
Lung Neoplasms
cells
docetaxel
adjuvants
cell lines
taxane
Cell Line
Taxoids
Biomarkers
MicroRNAs
microRNA
Computer Simulation
Modulators
biomarkers

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Du, L., Subauste, M. C., DeSevo, C., Zhao, Z., Baker, M., Borkowski, R., ... Pertsemlidis, A. (2012). miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers. PLoS One, 7(6), [e39167]. https://doi.org/10.1371/journal.pone.0039167

miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers. / Du, Liqin; Subauste, Maria C.; DeSevo, Christopher; Zhao, Zhenze; Baker, Michael; Borkowski, Robert; Schageman, Jeoffrey J.; Greer, Rachel; Yang, Chin Rang; Suraokar, Milind; Wistuba, Ignacio I.; Gazdar, Adi F.; Minna, John D.; Pertsemlidis, Alexander.

In: PLoS One, Vol. 7, No. 6, e39167, 18.06.2012.

Research output: Contribution to journalArticle

Du, L, Subauste, MC, DeSevo, C, Zhao, Z, Baker, M, Borkowski, R, Schageman, JJ, Greer, R, Yang, CR, Suraokar, M, Wistuba, II, Gazdar, AF, Minna, JD & Pertsemlidis, A 2012, 'miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers', PLoS One, vol. 7, no. 6, e39167. https://doi.org/10.1371/journal.pone.0039167
Du, Liqin ; Subauste, Maria C. ; DeSevo, Christopher ; Zhao, Zhenze ; Baker, Michael ; Borkowski, Robert ; Schageman, Jeoffrey J. ; Greer, Rachel ; Yang, Chin Rang ; Suraokar, Milind ; Wistuba, Ignacio I. ; Gazdar, Adi F. ; Minna, John D. ; Pertsemlidis, Alexander. / miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers. In: PLoS One. 2012 ; Vol. 7, No. 6.
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abstract = "NSCLC (non-small cell lung cancer) often exhibits resistance to paclitaxel treatment. Identifying the elements regulating paclitaxel response will advance efforts to overcome such resistance in NSCLC therapy. Using in vitro approaches, we demonstrated that over-expression of the microRNA miR-337-3p sensitizes NCI-H1155 cells to paclitaxel, and that miR-337-3p mimic has a general effect on paclitaxel response in NSCLC cell lines, which may provide a novel adjuvant strategy to paclitaxel in the treatment of lung cancer. By combining in vitro and in silico approaches, we identified STAT3 and RAP1A as direct targets that mediate the effect of miR-337-3p on paclitaxel sensitivity. Further investigation showed that miR-337-3p mimic also sensitizes cells to docetaxel, another member of the taxane family, and that STAT3 levels are significantly correlated with taxane resistance in lung cancer cell lines, suggesting that endogenous STAT3 expression is a determinant of intrinsic taxane resistance in lung cancer. The identification of a miR-337-3p as a modulator of cellular response to taxanes, and STAT3 and RAP1A as regulatory targets which mediate that response, defines a novel regulatory pathway modulating paclitaxel sensitivity in lung cancer cells, which may provide novel adjuvant strategies along with paclitaxel in the treatment of lung cancer and may also provide biomarkers for predicting paclitaxel response in NSCLC.",
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AU - Zhao, Zhenze

AU - Baker, Michael

AU - Borkowski, Robert

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AU - Greer, Rachel

AU - Yang, Chin Rang

AU - Suraokar, Milind

AU - Wistuba, Ignacio I.

AU - Gazdar, Adi F.

AU - Minna, John D.

AU - Pertsemlidis, Alexander

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