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Prognostic and predictive values of long non-coding RNA LINC00472 in breast cancer.

Shen Y, Katsaros D, Loo LW, Hernandez BY, Chong C, Canuto EM, Biglia N, Lu L, Risch H, Chu WM, Yu H - Oncotarget (2015)

Bottom Line: Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes.Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression.High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors.

View Article: PubMed Central - PubMed

Affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.

ABSTRACT
LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer.

No MeSH data available.


Related in: MedlinePlus

Effect of LINC00472 expression on breast cancer cell proliferationA. GFP fluorescence images in MCF7 and SKBR3 cells transfected with pCDH or pCDH_LINC00472 vectors. B. RT-qPCR results of LINC00472 expression in MCF7 and SKBR3 cells transfected with pCDH or pCDH_LINC00472 or mock transfected. C. Cell growth inhibition by LINC00472 in MCF7 cells. Twenty hours after seeding in 96-well plates, cells were transiently transfected with pCDH or pCDH_LINC00472 vectors, and kept in culture for up to 96 hours. Absorbance at 450nm of each well, which was directly proportional to the number of living cells in the well, was measured by SpectraMax M3 Multimode Plate Reader. The y axis showed the relative absorbance of corresponding wells from different days compared to that from day 0. Error bars represent SEM, n = 15. P values were determined by the Mann-Whitney U test. D. Inhibition of cell growth by LINC00472 in SKBR3 cells. The experiment and analysis are same as to those in C.
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Figure 4: Effect of LINC00472 expression on breast cancer cell proliferationA. GFP fluorescence images in MCF7 and SKBR3 cells transfected with pCDH or pCDH_LINC00472 vectors. B. RT-qPCR results of LINC00472 expression in MCF7 and SKBR3 cells transfected with pCDH or pCDH_LINC00472 or mock transfected. C. Cell growth inhibition by LINC00472 in MCF7 cells. Twenty hours after seeding in 96-well plates, cells were transiently transfected with pCDH or pCDH_LINC00472 vectors, and kept in culture for up to 96 hours. Absorbance at 450nm of each well, which was directly proportional to the number of living cells in the well, was measured by SpectraMax M3 Multimode Plate Reader. The y axis showed the relative absorbance of corresponding wells from different days compared to that from day 0. Error bars represent SEM, n = 15. P values were determined by the Mann-Whitney U test. D. Inhibition of cell growth by LINC00472 in SKBR3 cells. The experiment and analysis are same as to those in C.

Mentions: To examine the effect of LINC00472 on breast cancer cells, we analyzed LINC00472 expression in MCF7 and SKBR3, and found that the expression was low in these cell lines. We created an expression vector, pCDH_LINC00472 (Supplementary Figure S4), and transfected the vector into breast cancer cells to increase LINC00472 expression. The transfection was successful based on the GFP signal and RT-qPCR analysis (Figure 4). Cell proliferation assays showed that LINC00472 expression significantly inhibited tumor cell growth (Figure 4). Furthermore, in the cell migration experiments, we found that both MCF7 and SKBR3 cell lines exhibited reduced migration after being transfected with LINC00472 expressing vectors (Figure 5). These in vitro experiments suggest that increased LINC00472 expression may suppress tumor cell proliferation and migration, which is consistent with the findings of our clinical studies.


Prognostic and predictive values of long non-coding RNA LINC00472 in breast cancer.

Shen Y, Katsaros D, Loo LW, Hernandez BY, Chong C, Canuto EM, Biglia N, Lu L, Risch H, Chu WM, Yu H - Oncotarget (2015)

Effect of LINC00472 expression on breast cancer cell proliferationA. GFP fluorescence images in MCF7 and SKBR3 cells transfected with pCDH or pCDH_LINC00472 vectors. B. RT-qPCR results of LINC00472 expression in MCF7 and SKBR3 cells transfected with pCDH or pCDH_LINC00472 or mock transfected. C. Cell growth inhibition by LINC00472 in MCF7 cells. Twenty hours after seeding in 96-well plates, cells were transiently transfected with pCDH or pCDH_LINC00472 vectors, and kept in culture for up to 96 hours. Absorbance at 450nm of each well, which was directly proportional to the number of living cells in the well, was measured by SpectraMax M3 Multimode Plate Reader. The y axis showed the relative absorbance of corresponding wells from different days compared to that from day 0. Error bars represent SEM, n = 15. P values were determined by the Mann-Whitney U test. D. Inhibition of cell growth by LINC00472 in SKBR3 cells. The experiment and analysis are same as to those in C.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4496168&req=5

Figure 4: Effect of LINC00472 expression on breast cancer cell proliferationA. GFP fluorescence images in MCF7 and SKBR3 cells transfected with pCDH or pCDH_LINC00472 vectors. B. RT-qPCR results of LINC00472 expression in MCF7 and SKBR3 cells transfected with pCDH or pCDH_LINC00472 or mock transfected. C. Cell growth inhibition by LINC00472 in MCF7 cells. Twenty hours after seeding in 96-well plates, cells were transiently transfected with pCDH or pCDH_LINC00472 vectors, and kept in culture for up to 96 hours. Absorbance at 450nm of each well, which was directly proportional to the number of living cells in the well, was measured by SpectraMax M3 Multimode Plate Reader. The y axis showed the relative absorbance of corresponding wells from different days compared to that from day 0. Error bars represent SEM, n = 15. P values were determined by the Mann-Whitney U test. D. Inhibition of cell growth by LINC00472 in SKBR3 cells. The experiment and analysis are same as to those in C.
Mentions: To examine the effect of LINC00472 on breast cancer cells, we analyzed LINC00472 expression in MCF7 and SKBR3, and found that the expression was low in these cell lines. We created an expression vector, pCDH_LINC00472 (Supplementary Figure S4), and transfected the vector into breast cancer cells to increase LINC00472 expression. The transfection was successful based on the GFP signal and RT-qPCR analysis (Figure 4). Cell proliferation assays showed that LINC00472 expression significantly inhibited tumor cell growth (Figure 4). Furthermore, in the cell migration experiments, we found that both MCF7 and SKBR3 cell lines exhibited reduced migration after being transfected with LINC00472 expressing vectors (Figure 5). These in vitro experiments suggest that increased LINC00472 expression may suppress tumor cell proliferation and migration, which is consistent with the findings of our clinical studies.

Bottom Line: Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes.Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression.High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors.

View Article: PubMed Central - PubMed

Affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.

ABSTRACT
LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer.

No MeSH data available.


Related in: MedlinePlus