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Long non-coding RNA ROR decoys gene-specific histone methylation to promote tumorigenesis.

Fan J, Xing Y, Wen X, Jia R, Ni H, He J, Ding X, Pan H, Qian G, Ge S, Hoffman AR, Zhang H, Fan X - Genome Biol. (2015)

Bottom Line: Suppression of ROR in tumors results in silencing of TESC expression, and G9A-mediated histone H3K9 methylation in the TESC promoter is restored, which significantly reduces tumor growth and metastasis.Without ROR silencing, TESC knockdown presents consistent and significant reductions in tumor progression.Our results reveal a novel mechanism by which ROR may serve as a decoy oncoRNA that blocks binding surfaces, preventing the recruitment of histone modifying enzymes, thereby specifying a new pattern of histone modifications that promote tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, P. R. China.

ABSTRACT

Background: Long non-coding RNAs (lncRNAs) are not translated into proteins and were initially considered to be part of the 'dark matter' of the genome. Recently, it has been shown that lncRNAs play a role in the recruitment of chromatin modifying complexes and can influence gene expression. However, it is unknown if lncRNAs function in a similar way in cancer.

Results: Here, we show that the lncRNA ROR occupies and activates the TESC promoter by repelling the histone G9A methyltransferase and promoting the release of histone H3K9 methylation. Suppression of ROR in tumors results in silencing of TESC expression, and G9A-mediated histone H3K9 methylation in the TESC promoter is restored, which significantly reduces tumor growth and metastasis. Without ROR silencing, TESC knockdown presents consistent and significant reductions in tumor progression.

Conclusions: Our results reveal a novel mechanism by which ROR may serve as a decoy oncoRNA that blocks binding surfaces, preventing the recruitment of histone modifying enzymes, thereby specifying a new pattern of histone modifications that promote tumorigenesis.

No MeSH data available.


Related in: MedlinePlus

ROR modulates tumor growth and metastasis. a, b MTT assay showing tumor cell growth after ROR knock-down. Cell growth was obviously restrained at day 3 in ROR-silenced AGS and HT29 cells. The absorbance values were detected at 24 h, 48 h, and 72 h, the control was arbitrarily set at 100 % on day 1. c, d The migratory ability of ROR-silenced tumor cells. The ability to metastasize in ROR-silenced tumor cells was remarkably reduced compared with the untreated control cells. The 570 nm absorbance values of the control were set at 1. The migration detection was conducted at 24 h for AGS cells (c) and 48 h for HT29 cells (d). All of the data are presented as the mean ± SD. *P <0.05: compared with the control and mock. e Images of a soft agar tumor colony. Few visible colonies were observed in the ROR knockdown tumor cells. Bars: 100 μm. f Colony count statistics demonstrate tumor formation ability. Colony count statistics showed a significant reduction in ROR-silenced AGS and HT29 cells. Colony numbers were determined from three independent soft agar plates. All of the data are presented as the mean ± SD. *P <0.05: compared with the control and mock
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Fig2: ROR modulates tumor growth and metastasis. a, b MTT assay showing tumor cell growth after ROR knock-down. Cell growth was obviously restrained at day 3 in ROR-silenced AGS and HT29 cells. The absorbance values were detected at 24 h, 48 h, and 72 h, the control was arbitrarily set at 100 % on day 1. c, d The migratory ability of ROR-silenced tumor cells. The ability to metastasize in ROR-silenced tumor cells was remarkably reduced compared with the untreated control cells. The 570 nm absorbance values of the control were set at 1. The migration detection was conducted at 24 h for AGS cells (c) and 48 h for HT29 cells (d). All of the data are presented as the mean ± SD. *P <0.05: compared with the control and mock. e Images of a soft agar tumor colony. Few visible colonies were observed in the ROR knockdown tumor cells. Bars: 100 μm. f Colony count statistics demonstrate tumor formation ability. Colony count statistics showed a significant reduction in ROR-silenced AGS and HT29 cells. Colony numbers were determined from three independent soft agar plates. All of the data are presented as the mean ± SD. *P <0.05: compared with the control and mock

Mentions: Whether the tumor characteristics were significantly altered after ROR knockdown was then investigated. In an MTT assay, tumor cell growth showed an approximately two-fold decrease at day 3 in all ROR-silenced AGS and HT29 cells (Fig. 2a and b, triangle and inverted triangle), whereas the control (Fig. 2a and b, circle) and mock (Fig. 2a and b, Square) cells retained higher cell viability.Fig. 2


Long non-coding RNA ROR decoys gene-specific histone methylation to promote tumorigenesis.

Fan J, Xing Y, Wen X, Jia R, Ni H, He J, Ding X, Pan H, Qian G, Ge S, Hoffman AR, Zhang H, Fan X - Genome Biol. (2015)

ROR modulates tumor growth and metastasis. a, b MTT assay showing tumor cell growth after ROR knock-down. Cell growth was obviously restrained at day 3 in ROR-silenced AGS and HT29 cells. The absorbance values were detected at 24 h, 48 h, and 72 h, the control was arbitrarily set at 100 % on day 1. c, d The migratory ability of ROR-silenced tumor cells. The ability to metastasize in ROR-silenced tumor cells was remarkably reduced compared with the untreated control cells. The 570 nm absorbance values of the control were set at 1. The migration detection was conducted at 24 h for AGS cells (c) and 48 h for HT29 cells (d). All of the data are presented as the mean ± SD. *P <0.05: compared with the control and mock. e Images of a soft agar tumor colony. Few visible colonies were observed in the ROR knockdown tumor cells. Bars: 100 μm. f Colony count statistics demonstrate tumor formation ability. Colony count statistics showed a significant reduction in ROR-silenced AGS and HT29 cells. Colony numbers were determined from three independent soft agar plates. All of the data are presented as the mean ± SD. *P <0.05: compared with the control and mock
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4499915&req=5

Fig2: ROR modulates tumor growth and metastasis. a, b MTT assay showing tumor cell growth after ROR knock-down. Cell growth was obviously restrained at day 3 in ROR-silenced AGS and HT29 cells. The absorbance values were detected at 24 h, 48 h, and 72 h, the control was arbitrarily set at 100 % on day 1. c, d The migratory ability of ROR-silenced tumor cells. The ability to metastasize in ROR-silenced tumor cells was remarkably reduced compared with the untreated control cells. The 570 nm absorbance values of the control were set at 1. The migration detection was conducted at 24 h for AGS cells (c) and 48 h for HT29 cells (d). All of the data are presented as the mean ± SD. *P <0.05: compared with the control and mock. e Images of a soft agar tumor colony. Few visible colonies were observed in the ROR knockdown tumor cells. Bars: 100 μm. f Colony count statistics demonstrate tumor formation ability. Colony count statistics showed a significant reduction in ROR-silenced AGS and HT29 cells. Colony numbers were determined from three independent soft agar plates. All of the data are presented as the mean ± SD. *P <0.05: compared with the control and mock
Mentions: Whether the tumor characteristics were significantly altered after ROR knockdown was then investigated. In an MTT assay, tumor cell growth showed an approximately two-fold decrease at day 3 in all ROR-silenced AGS and HT29 cells (Fig. 2a and b, triangle and inverted triangle), whereas the control (Fig. 2a and b, circle) and mock (Fig. 2a and b, Square) cells retained higher cell viability.Fig. 2

Bottom Line: Suppression of ROR in tumors results in silencing of TESC expression, and G9A-mediated histone H3K9 methylation in the TESC promoter is restored, which significantly reduces tumor growth and metastasis.Without ROR silencing, TESC knockdown presents consistent and significant reductions in tumor progression.Our results reveal a novel mechanism by which ROR may serve as a decoy oncoRNA that blocks binding surfaces, preventing the recruitment of histone modifying enzymes, thereby specifying a new pattern of histone modifications that promote tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, P. R. China.

ABSTRACT

Background: Long non-coding RNAs (lncRNAs) are not translated into proteins and were initially considered to be part of the 'dark matter' of the genome. Recently, it has been shown that lncRNAs play a role in the recruitment of chromatin modifying complexes and can influence gene expression. However, it is unknown if lncRNAs function in a similar way in cancer.

Results: Here, we show that the lncRNA ROR occupies and activates the TESC promoter by repelling the histone G9A methyltransferase and promoting the release of histone H3K9 methylation. Suppression of ROR in tumors results in silencing of TESC expression, and G9A-mediated histone H3K9 methylation in the TESC promoter is restored, which significantly reduces tumor growth and metastasis. Without ROR silencing, TESC knockdown presents consistent and significant reductions in tumor progression.

Conclusions: Our results reveal a novel mechanism by which ROR may serve as a decoy oncoRNA that blocks binding surfaces, preventing the recruitment of histone modifying enzymes, thereby specifying a new pattern of histone modifications that promote tumorigenesis.

No MeSH data available.


Related in: MedlinePlus