MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration

Shilpi Arora, Aarati R. Ranade, Nhan Tran, Sara Nasser, Shravan Sridhar, Ronald L. Korn, Julianna T D Ross, Harshil Dhruv, Kristen M. Foss, Zita Sibenaller, Timothy Ryken, Michael Gotway, Seungchan Kim, Glen J. Weiss

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Brain metastasis (BM) can affect ∼ 25% of nonsmall cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been disappointing. microRNAs (miRNAs) regulate the expression of target mRNAs. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which make them a powerful tool for early detection of disease, risk assessment, and prognosis. We investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from seven patients with BM (BM+) and six without BM (BM-). Using t-test and further qRT-PCR validation, eight miRNAs were confirmed to be significantly differentially expressed. Of these, expression of miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM- patients. This classifier was used on a validation cohort (n = 15), and it correctly classified 12/15 patients. Gene expression analysis comparing A549 parental and A549 cells stably transfected to over-express miR-328 (A549-328) identified several significantly differentially expressed genes. PRKCA was one of the genes over-expressed in A549-328 cells. Additionally, A549-328 cells had significantly increased cell migration compared to A549 cells, which was significantly reduced upon PRKCA knockdown. In summary, miR-328 has a role in conferring migratory potential to NSCLC cells working in part through PRKCA and with further corroboration in additional independent cohorts, these miRNAs may be incorporated into clinical treatment decision making to stratify NSCLC patients at higher risk for developing BM.

Original languageEnglish (US)
Pages (from-to)2621-2631
Number of pages11
JournalInternational Journal of Cancer
Volume129
Issue number11
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Fingerprint

MicroRNAs
Non-Small Cell Lung Carcinoma
Brain Neoplasms
Neoplasm Metastasis
Brain
Genes
Cell Movement
Early Diagnosis
Biomarkers
Gene Expression
Polymerase Chain Reaction
Messenger RNA
A549 Cells

Keywords

  • biomarker
  • brain metastasis
  • microRNA
  • migration
  • non-small cell lung cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration. / Arora, Shilpi; Ranade, Aarati R.; Tran, Nhan; Nasser, Sara; Sridhar, Shravan; Korn, Ronald L.; Ross, Julianna T D; Dhruv, Harshil; Foss, Kristen M.; Sibenaller, Zita; Ryken, Timothy; Gotway, Michael; Kim, Seungchan; Weiss, Glen J.

In: International Journal of Cancer, Vol. 129, No. 11, 01.12.2011, p. 2621-2631.

Research output: Contribution to journalArticle

Arora, S, Ranade, AR, Tran, N, Nasser, S, Sridhar, S, Korn, RL, Ross, JTD, Dhruv, H, Foss, KM, Sibenaller, Z, Ryken, T, Gotway, M, Kim, S & Weiss, GJ 2011, 'MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration', International Journal of Cancer, vol. 129, no. 11, pp. 2621-2631. https://doi.org/10.1002/ijc.25939
Arora, Shilpi ; Ranade, Aarati R. ; Tran, Nhan ; Nasser, Sara ; Sridhar, Shravan ; Korn, Ronald L. ; Ross, Julianna T D ; Dhruv, Harshil ; Foss, Kristen M. ; Sibenaller, Zita ; Ryken, Timothy ; Gotway, Michael ; Kim, Seungchan ; Weiss, Glen J. / MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration. In: International Journal of Cancer. 2011 ; Vol. 129, No. 11. pp. 2621-2631.
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AU - Arora, Shilpi

AU - Ranade, Aarati R.

AU - Tran, Nhan

AU - Nasser, Sara

AU - Sridhar, Shravan

AU - Korn, Ronald L.

AU - Ross, Julianna T D

AU - Dhruv, Harshil

AU - Foss, Kristen M.

AU - Sibenaller, Zita

AU - Ryken, Timothy

AU - Gotway, Michael

AU - Kim, Seungchan

AU - Weiss, Glen J.

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N2 - Brain metastasis (BM) can affect ∼ 25% of nonsmall cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been disappointing. microRNAs (miRNAs) regulate the expression of target mRNAs. miRNAs play a role in regulating a variety of targets and, consequently, multiple pathways, which make them a powerful tool for early detection of disease, risk assessment, and prognosis. We investigated miRNAs that may serve as biomarkers to differentiate between NSCLC patients with and without BM. miRNA microarray profiling was performed on samples from clinically matched NSCLC from seven patients with BM (BM+) and six without BM (BM-). Using t-test and further qRT-PCR validation, eight miRNAs were confirmed to be significantly differentially expressed. Of these, expression of miR-328 and miR-330-3p were able to correctly classify BM+ vs. BM- patients. This classifier was used on a validation cohort (n = 15), and it correctly classified 12/15 patients. Gene expression analysis comparing A549 parental and A549 cells stably transfected to over-express miR-328 (A549-328) identified several significantly differentially expressed genes. PRKCA was one of the genes over-expressed in A549-328 cells. Additionally, A549-328 cells had significantly increased cell migration compared to A549 cells, which was significantly reduced upon PRKCA knockdown. In summary, miR-328 has a role in conferring migratory potential to NSCLC cells working in part through PRKCA and with further corroboration in additional independent cohorts, these miRNAs may be incorporated into clinical treatment decision making to stratify NSCLC patients at higher risk for developing BM.

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