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A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies.

Sun J, Li W, Sun Y, Yu D, Wen X, Wang H, Cui J, Wang G, Hoffman AR, Hu JF - Nucleic Acids Res. (2014)

Bottom Line: Using both reverse transcription-associated trap and chromatin conformation capture assays, we demonstrate that this lncRNA interacts with chromatin DNA and is involved in the formation of an intrachromosomal enhancer/promoter loop.In addition, IRAIN was downregulated both in leukemia cell lines and in blood obtained from high-risk AML patients.These data identify IRAIN as a new imprinted lncRNA that is involved in long-range DNA interactions.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.

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Downregulation of the IRAIN lncRNA in tumor cell lines and AML tissues. (A) Expression patterns of IRAIN and IGF1R in tumor cell lines. β-Actin was used in the internal PCR control for qPCR. Data are represented as mean ± SD. The relative expression was determined by normalizing the qPCR signals over that of normal HSC2 cells. *P < 0.05 as compared with the IGF1R coding RNA. (B) Expression of IRAIN lncRNA in AML patients. HR, LR: AML with high and low risk (AML-HR, n = 16; AML-LR, n = 18; and normal, n = 5). Data are represented as mean ± SD. *P < 0.05 as compared with the AML high-risk patients. (C) Inhibition of cell migration by 5.4 kb IRAIN lncRNA. Lentiviruses containing the full-length lncRNA and the vector control were transduced into MDA 231 cells. Stable cell clones were used to test the cell migration using transwell assay. Data are represented as mean ± SD. *P < 0.01 as compared with the vector control.
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Figure 6: Downregulation of the IRAIN lncRNA in tumor cell lines and AML tissues. (A) Expression patterns of IRAIN and IGF1R in tumor cell lines. β-Actin was used in the internal PCR control for qPCR. Data are represented as mean ± SD. The relative expression was determined by normalizing the qPCR signals over that of normal HSC2 cells. *P < 0.05 as compared with the IGF1R coding RNA. (B) Expression of IRAIN lncRNA in AML patients. HR, LR: AML with high and low risk (AML-HR, n = 16; AML-LR, n = 18; and normal, n = 5). Data are represented as mean ± SD. *P < 0.05 as compared with the AML high-risk patients. (C) Inhibition of cell migration by 5.4 kb IRAIN lncRNA. Lentiviruses containing the full-length lncRNA and the vector control were transduced into MDA 231 cells. Stable cell clones were used to test the cell migration using transwell assay. Data are represented as mean ± SD. *P < 0.01 as compared with the vector control.

Mentions: IGF1R is frequently overexpressed in human tumors. We were curious if IRAIN was dysregulated in tumors as well. We first used real-time PCR to compare the abundance of IRAIN lncRNA and IGF1R coding RNA transcripts in hematopoietic cell lines. Using a normal hematopoietic stem cell line HSC2 as a standard, we found that IRAIN was downregulated in leukemia cell lines as compared with the IGF1R sense coding RNA (Figure 6A).


A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies.

Sun J, Li W, Sun Y, Yu D, Wen X, Wang H, Cui J, Wang G, Hoffman AR, Hu JF - Nucleic Acids Res. (2014)

Downregulation of the IRAIN lncRNA in tumor cell lines and AML tissues. (A) Expression patterns of IRAIN and IGF1R in tumor cell lines. β-Actin was used in the internal PCR control for qPCR. Data are represented as mean ± SD. The relative expression was determined by normalizing the qPCR signals over that of normal HSC2 cells. *P < 0.05 as compared with the IGF1R coding RNA. (B) Expression of IRAIN lncRNA in AML patients. HR, LR: AML with high and low risk (AML-HR, n = 16; AML-LR, n = 18; and normal, n = 5). Data are represented as mean ± SD. *P < 0.05 as compared with the AML high-risk patients. (C) Inhibition of cell migration by 5.4 kb IRAIN lncRNA. Lentiviruses containing the full-length lncRNA and the vector control were transduced into MDA 231 cells. Stable cell clones were used to test the cell migration using transwell assay. Data are represented as mean ± SD. *P < 0.01 as compared with the vector control.
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Figure 6: Downregulation of the IRAIN lncRNA in tumor cell lines and AML tissues. (A) Expression patterns of IRAIN and IGF1R in tumor cell lines. β-Actin was used in the internal PCR control for qPCR. Data are represented as mean ± SD. The relative expression was determined by normalizing the qPCR signals over that of normal HSC2 cells. *P < 0.05 as compared with the IGF1R coding RNA. (B) Expression of IRAIN lncRNA in AML patients. HR, LR: AML with high and low risk (AML-HR, n = 16; AML-LR, n = 18; and normal, n = 5). Data are represented as mean ± SD. *P < 0.05 as compared with the AML high-risk patients. (C) Inhibition of cell migration by 5.4 kb IRAIN lncRNA. Lentiviruses containing the full-length lncRNA and the vector control were transduced into MDA 231 cells. Stable cell clones were used to test the cell migration using transwell assay. Data are represented as mean ± SD. *P < 0.01 as compared with the vector control.
Mentions: IGF1R is frequently overexpressed in human tumors. We were curious if IRAIN was dysregulated in tumors as well. We first used real-time PCR to compare the abundance of IRAIN lncRNA and IGF1R coding RNA transcripts in hematopoietic cell lines. Using a normal hematopoietic stem cell line HSC2 as a standard, we found that IRAIN was downregulated in leukemia cell lines as compared with the IGF1R sense coding RNA (Figure 6A).

Bottom Line: Using both reverse transcription-associated trap and chromatin conformation capture assays, we demonstrate that this lncRNA interacts with chromatin DNA and is involved in the formation of an intrachromosomal enhancer/promoter loop.In addition, IRAIN was downregulated both in leukemia cell lines and in blood obtained from high-risk AML patients.These data identify IRAIN as a new imprinted lncRNA that is involved in long-range DNA interactions.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061, PR China Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.

Show MeSH
Related in: MedlinePlus