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An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL/COMPASS-like complexes.

He X, Chen X, Zhang X, Duan X, Pan T, Hu Q, Zhang Y, Zhong F, Liu J, Zhang H, Luo J, Wu K, Peng G, Luo H, Zhang L, Li X, Zhang H - Nucleic Acids Res. (2015)

Bottom Line: However, its function in the mammalian somatic cells remains unknown.Interestingly, the PIWIL1/4 proteins, which bind with this piRNA, directly interact with WDR5, resulting in a site-specific recruitment of the hCOMPASS-like complexes containing at least MLL3 and UTX (KDM6A).We have indicated a novel pathway for piRNAs to specially activate gene expression.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.

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Gas5-derived small RNA (pi-sno75) specifically upregulates TRAIL expression in breast cancer cells. (A) The mRNA profiling microarray analysis. The gene expression scatterplot of the piRNAs mixture group versus that of the control group was shown. Significantly downregulated genes were shown in green, while upregulated genes in red. (B) MCF7 cells were transfected with piRNAs derived from GAS5 respectively for 48h, TRAIL mRNA levels were analysed by quantitative RT-PCR (qRT-PCR) and normalized to GAPDH levels. (C) MCF7 cells were transfected with pi-sno75 at different concentrations. The qRT-PCR was performed to analyse the effect of pi-sno75 on TRAIL expression. (D) MCF7 cells were transfected with pi-sno75 and piNC for 48h, western blot was performed to analyse TRAIL protein expression. (E) In MCF7 cells transfected with pi-sno75, the mRNA levels of TRAIL and other genes were determined by qRT-PCR. Bar graphs in (B), (C) and (E) represent mean ± SD (n = 3).
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Figure 2: Gas5-derived small RNA (pi-sno75) specifically upregulates TRAIL expression in breast cancer cells. (A) The mRNA profiling microarray analysis. The gene expression scatterplot of the piRNAs mixture group versus that of the control group was shown. Significantly downregulated genes were shown in green, while upregulated genes in red. (B) MCF7 cells were transfected with piRNAs derived from GAS5 respectively for 48h, TRAIL mRNA levels were analysed by quantitative RT-PCR (qRT-PCR) and normalized to GAPDH levels. (C) MCF7 cells were transfected with pi-sno75 at different concentrations. The qRT-PCR was performed to analyse the effect of pi-sno75 on TRAIL expression. (D) MCF7 cells were transfected with pi-sno75 and piNC for 48h, western blot was performed to analyse TRAIL protein expression. (E) In MCF7 cells transfected with pi-sno75, the mRNA levels of TRAIL and other genes were determined by qRT-PCR. Bar graphs in (B), (C) and (E) represent mean ± SD (n = 3).

Mentions: The quantitative analysis of GAS5-derived small RNAs from clinical breast samples showed that the expressions of pi-snoRNAs, as well as the corresponding snoRNAs, were significantly lower in cancer tissues than in adjacent normal tissues (Figure 1C and Supplementary Figure S2A), which was in consistence with that of GAS5 (24). To investigate the function of these small RNAs in breast cancer cells, we transfected a mixture of the five chemically synthesized single-stranded piRNAs, including pi-sno44/74/75/78/81, into MCF7 cells and detected the gene expression by microarray. Approximate 290 genes whose expression changed significantly were filtered with a fold-change >2 (Figure 2A and Supplementary Table S3). We noticed that a group of piRNA-affected genes was related to the cancer-associated gene ontology (GO) terms, such as cell death or proliferation biological processes. Among these genes, TRAIL (also known as TNFSF10 and Apo2L) was significantly upregulated by the piRNAs’ mixture. TRAIL is a tumor-specific suppressor that induces apoptosis in a broad spectrum of cancer cells but not in normal cells (29).


An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL/COMPASS-like complexes.

He X, Chen X, Zhang X, Duan X, Pan T, Hu Q, Zhang Y, Zhong F, Liu J, Zhang H, Luo J, Wu K, Peng G, Luo H, Zhang L, Li X, Zhang H - Nucleic Acids Res. (2015)

Gas5-derived small RNA (pi-sno75) specifically upregulates TRAIL expression in breast cancer cells. (A) The mRNA profiling microarray analysis. The gene expression scatterplot of the piRNAs mixture group versus that of the control group was shown. Significantly downregulated genes were shown in green, while upregulated genes in red. (B) MCF7 cells were transfected with piRNAs derived from GAS5 respectively for 48h, TRAIL mRNA levels were analysed by quantitative RT-PCR (qRT-PCR) and normalized to GAPDH levels. (C) MCF7 cells were transfected with pi-sno75 at different concentrations. The qRT-PCR was performed to analyse the effect of pi-sno75 on TRAIL expression. (D) MCF7 cells were transfected with pi-sno75 and piNC for 48h, western blot was performed to analyse TRAIL protein expression. (E) In MCF7 cells transfected with pi-sno75, the mRNA levels of TRAIL and other genes were determined by qRT-PCR. Bar graphs in (B), (C) and (E) represent mean ± SD (n = 3).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4402533&req=5

Figure 2: Gas5-derived small RNA (pi-sno75) specifically upregulates TRAIL expression in breast cancer cells. (A) The mRNA profiling microarray analysis. The gene expression scatterplot of the piRNAs mixture group versus that of the control group was shown. Significantly downregulated genes were shown in green, while upregulated genes in red. (B) MCF7 cells were transfected with piRNAs derived from GAS5 respectively for 48h, TRAIL mRNA levels were analysed by quantitative RT-PCR (qRT-PCR) and normalized to GAPDH levels. (C) MCF7 cells were transfected with pi-sno75 at different concentrations. The qRT-PCR was performed to analyse the effect of pi-sno75 on TRAIL expression. (D) MCF7 cells were transfected with pi-sno75 and piNC for 48h, western blot was performed to analyse TRAIL protein expression. (E) In MCF7 cells transfected with pi-sno75, the mRNA levels of TRAIL and other genes were determined by qRT-PCR. Bar graphs in (B), (C) and (E) represent mean ± SD (n = 3).
Mentions: The quantitative analysis of GAS5-derived small RNAs from clinical breast samples showed that the expressions of pi-snoRNAs, as well as the corresponding snoRNAs, were significantly lower in cancer tissues than in adjacent normal tissues (Figure 1C and Supplementary Figure S2A), which was in consistence with that of GAS5 (24). To investigate the function of these small RNAs in breast cancer cells, we transfected a mixture of the five chemically synthesized single-stranded piRNAs, including pi-sno44/74/75/78/81, into MCF7 cells and detected the gene expression by microarray. Approximate 290 genes whose expression changed significantly were filtered with a fold-change >2 (Figure 2A and Supplementary Table S3). We noticed that a group of piRNA-affected genes was related to the cancer-associated gene ontology (GO) terms, such as cell death or proliferation biological processes. Among these genes, TRAIL (also known as TNFSF10 and Apo2L) was significantly upregulated by the piRNAs’ mixture. TRAIL is a tumor-specific suppressor that induces apoptosis in a broad spectrum of cancer cells but not in normal cells (29).

Bottom Line: However, its function in the mammalian somatic cells remains unknown.Interestingly, the PIWIL1/4 proteins, which bind with this piRNA, directly interact with WDR5, resulting in a site-specific recruitment of the hCOMPASS-like complexes containing at least MLL3 and UTX (KDM6A).We have indicated a novel pathway for piRNAs to specially activate gene expression.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.

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Related in: MedlinePlus