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| Status |
Public on Apr 21, 2015 |
| Title |
The effect of miRNA-135b overexpression on the gene expression profile of LNCaP cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
MicroRNAs (miRNAs) regulate a wide range of cellular signaling pathways and biological processes in both physiological and pathological states such as cancer. We have previously identified miR-135b as a direct regulator of androgen receptor (AR) protein level in prostate cancer (PCa). We wanted to further explore the relationship of miR-135b to hormonal receptors, particularly estrogen receptor α (ERα). Here we show that miR-135b expression inversely correlates with ER protein in two independent breast cancer (BCa) patient cohorts (101 and 1302 samples) and with AR protein in 47 PCa patient samples. We identify ERα as a novel miR-135b target by demonstrating miR-135b binding to the 3’UTR of the ERα and decreased ERα protein and mRNA level in breast cancer cells upon miR-135b overexpression. miR-135b inhibits proliferation of hormone receptor positive cancer cell lines as shown by overexpression in ERα-positive BCa cells (MCF-7) and AR-positive PCa cells (LNCaP, 22Rv1) when grown in 2D. To identify other genes regulated by miR-135b we performed gene expression studies and found a potential link to the hypoxia-inducible factor-1α (HIF1α) pathway. We show that miR-135b influences the protein level of the inhibitor for hypoxia-inducible factor-1 (HIF1AN), which also demonstrated an inverse correlation with miR-135b in a cohort of breast tumor samples. Taken together, our study demonstrates that miR-135b regulates ERα, AR and HIF1AN protein levels and proliferation in ERα -positive breast and AR-positive-prostate cancer cells.
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| Overall design |
LNCaP cells were transfected with Ambion pre-miR™ construct for miR-135b or with pre-miR negative control #1 (scrambled pre-miR, Scr) at 20 nM, and incubated for 12h, 24h or 36h, in two biological repeats (B1 and B2)
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| Contributor(s) |
Aakula A, Leivonen S, Hintsanen P, Aittokallio T, Ceder Y, Børresen-Dale A, Perälä M, Östling P, Kallioniemi O |
| Citation(s) |
25907805 |
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| Submission date |
May 20, 2014 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Anna Aakula |
| E-mail(s) |
anna.aakula@fimm.fi
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| Organization name |
Institute for Molecular Medicine Finland, FIMM
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| Street address |
Tukholmankatu 8
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| City |
HELSINKI |
| ZIP/Postal code |
00290 |
| Country |
Finland |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA248178 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE57820_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE57820_non_normalized.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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