NFIX as a master regulator for lung cancer progression

Nor I.A. Rahman, Nor Azian Abdul Murad, Mohammad M. Mollah, A. Rahman A. Jamal, Roslan Harun

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

About 40% of lung cancer cases globally are diagnosed at the advanced stage. Lung cancer has a high mortality and overall survival in stage I disease is only 70%. This study was aimed at finding a candidate of transcription regulator that initiates the mechanism for metastasis by integrating computational and functional studies. The genes involved in lung cancer were retrieved using in silico software. 10 kb promoter sequences upstream were scanned for the master regulator. Transient transfection of shRNA NFIXs were conducted against A549 and NCI-H1299 cell lines. qRT-PCR and functional assays for cell proliferation, migration and invasion were carried out to validate the involvement of NFIX in metastasis. Genome-wide gene expression microarray using a HumanHT-12v4.0 Expression BeadChip Kit was performed to identify differentially expressed genes and construct a new regulatory network. The in silico analysis identified NFIX as a master regulator and is strongly associated with 17 genes involved in the migration and invasion pathways including IL6ST, TIMP1 and ITGB1. Silencing of NFIX showed reduced expression of IL6ST, TIMP1 and ITGB1 as well as the cellular proliferation, migration and invasion processes. The data was integrated with the in silico analyses to find the differentially expressed genes. Microarray analysis showed that 18 genes were expressed differentially in both cell lines after statistical analyses integration between t-test, LIMMA and ANOVA with Benjamini-Hochberg adjustment at p-value < 0.05. A transcriptional regulatory network was created using all 18 genes, the existing regulated genes including the new genes PTCH1, NFAT5 and GGCX that were found highly associated with NFIX, the master regulator of metastasis. This study suggests that NFIX is a promising target for therapeutic intervention that is expected to inhibit metastatic recurrence and improve survival rate.

Original languageEnglish
Article number540
JournalFrontiers in Pharmacology
Volume8
Issue numberAUG
DOIs
Publication statusPublished - 21 Aug 2017

Fingerprint

Lung Neoplasms
Genes
Computer Simulation
Neoplasm Metastasis
Cell Migration Assays
Cell Proliferation
Cell Line
Gene Regulatory Networks
Microarray Analysis
Small Interfering RNA
Transfection
Analysis of Variance
Software
Genome
Gene Expression
Recurrence
Polymerase Chain Reaction
Mortality

Keywords

  • Lung cancer
  • Master regulator
  • Metastasis
  • NFIX
  • Transcription factor
  • Transcriptional regulator

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

NFIX as a master regulator for lung cancer progression. / Rahman, Nor I.A.; Abdul Murad, Nor Azian; Mollah, Mohammad M.; A. Jamal, A. Rahman; Harun, Roslan.

In: Frontiers in Pharmacology, Vol. 8, No. AUG, 540, 21.08.2017.

Research output: Contribution to journalArticle

Rahman, Nor I.A. ; Abdul Murad, Nor Azian ; Mollah, Mohammad M. ; A. Jamal, A. Rahman ; Harun, Roslan. / NFIX as a master regulator for lung cancer progression. In: Frontiers in Pharmacology. 2017 ; Vol. 8, No. AUG.
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