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7SL RNA represses p53 translation by competing with HuR.

Abdelmohsen K, Panda AC, Kang MJ, Guo R, Kim J, Grammatikakis I, Yoon JH, Dudekula DB, Noh JH, Yang X, Martindale JL, Gorospe M - Nucleic Acids Res. (2014)

Bottom Line: The interaction of 7SL with TP53 mRNA reduced p53 translation, as determined by analyzing p53 expression levels, nascent p53 translation and TP53 mRNA association with polysomes.We propose that the competition between 7SL and HuR for binding to TP53 3'UTR contributes to determining the magnitude of p53 translation, in turn affecting p53 levels and the growth-suppressive function of p53.Our findings suggest that targeting 7SL may be effective in the treatment of cancers with reduced p53 levels.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA abdelmohsenk@mail.nih.gov.

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7SL is highly expressed in cancer tissues and is required for cell growth. (A) The abundance of 7SL in the tumor tissues (T) indicated (liver, lung, breast, stomach) and adjacent normal tissues (N) was measured by RT-qPCR analysis and normalized to 18S rRNA levels. (B) RT-qPCR analysis of 7SL levels 48 h after transfection of HeLa cells with Ctrl siRNA or 7SL siRNA. (C) Forty-eight hours after siRNA transfection of HeLa, Mia PaCa-2, HCT116 or RKO cells, cell numbers were measured using a hemocytometer and represented as % of cells relative to the Ctrl group. (D) Growth kinetics of HeLa cells transfected with Ctrl siRNA or 7SL siRNA. Cells were counted daily for 4 days. Data in (B)–(D) are the means ± S.D. from three independent experiments.
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Figure 1: 7SL is highly expressed in cancer tissues and is required for cell growth. (A) The abundance of 7SL in the tumor tissues (T) indicated (liver, lung, breast, stomach) and adjacent normal tissues (N) was measured by RT-qPCR analysis and normalized to 18S rRNA levels. (B) RT-qPCR analysis of 7SL levels 48 h after transfection of HeLa cells with Ctrl siRNA or 7SL siRNA. (C) Forty-eight hours after siRNA transfection of HeLa, Mia PaCa-2, HCT116 or RKO cells, cell numbers were measured using a hemocytometer and represented as % of cells relative to the Ctrl group. (D) Growth kinetics of HeLa cells transfected with Ctrl siRNA or 7SL siRNA. Cells were counted daily for 4 days. Data in (B)–(D) are the means ± S.D. from three independent experiments.

Mentions: The ncRNA 7SL, as well as the related ncRNA BC200, were shown to be widely upregulated in various cancer types (21,22). In agreement with this finding, RT followed by real-time qPCR analysis revealed higher 7SL levels in various tumor (T) tissues (liver, lung, breast, stomach) than in normal (N) adjacent tissues (Figure 1A; similar results were obtained by northern blot analysis of other N and T pairs, Supplementary Figure S1). To study the impact of 7SL on cancer cells, we tested the effect of knocking down 7SL levels in different cancer cell lines. As shown (Figure 1B), 48 h after transfecting HeLa cells (cervical carcinoma) with 7SL siRNA, 7SL levels were reduced by ∼60% compared to control cells. Silencing 7SL significantly reduced cell number in a variety of cultured cancer cell types, including HeLa cells, pancreatic carcinoma (Mia PaCa-2) and colon cancer (HCT116 and RKO) cell lines, and repressed HeLa cell growth (Figure 1C and D). Together, these data indicate that 7SL is highly expressed in cancer cells and enhanced cancer cell growth.


7SL RNA represses p53 translation by competing with HuR.

Abdelmohsen K, Panda AC, Kang MJ, Guo R, Kim J, Grammatikakis I, Yoon JH, Dudekula DB, Noh JH, Yang X, Martindale JL, Gorospe M - Nucleic Acids Res. (2014)

7SL is highly expressed in cancer tissues and is required for cell growth. (A) The abundance of 7SL in the tumor tissues (T) indicated (liver, lung, breast, stomach) and adjacent normal tissues (N) was measured by RT-qPCR analysis and normalized to 18S rRNA levels. (B) RT-qPCR analysis of 7SL levels 48 h after transfection of HeLa cells with Ctrl siRNA or 7SL siRNA. (C) Forty-eight hours after siRNA transfection of HeLa, Mia PaCa-2, HCT116 or RKO cells, cell numbers were measured using a hemocytometer and represented as % of cells relative to the Ctrl group. (D) Growth kinetics of HeLa cells transfected with Ctrl siRNA or 7SL siRNA. Cells were counted daily for 4 days. Data in (B)–(D) are the means ± S.D. from three independent experiments.
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Related In: Results  -  Collection

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Figure 1: 7SL is highly expressed in cancer tissues and is required for cell growth. (A) The abundance of 7SL in the tumor tissues (T) indicated (liver, lung, breast, stomach) and adjacent normal tissues (N) was measured by RT-qPCR analysis and normalized to 18S rRNA levels. (B) RT-qPCR analysis of 7SL levels 48 h after transfection of HeLa cells with Ctrl siRNA or 7SL siRNA. (C) Forty-eight hours after siRNA transfection of HeLa, Mia PaCa-2, HCT116 or RKO cells, cell numbers were measured using a hemocytometer and represented as % of cells relative to the Ctrl group. (D) Growth kinetics of HeLa cells transfected with Ctrl siRNA or 7SL siRNA. Cells were counted daily for 4 days. Data in (B)–(D) are the means ± S.D. from three independent experiments.
Mentions: The ncRNA 7SL, as well as the related ncRNA BC200, were shown to be widely upregulated in various cancer types (21,22). In agreement with this finding, RT followed by real-time qPCR analysis revealed higher 7SL levels in various tumor (T) tissues (liver, lung, breast, stomach) than in normal (N) adjacent tissues (Figure 1A; similar results were obtained by northern blot analysis of other N and T pairs, Supplementary Figure S1). To study the impact of 7SL on cancer cells, we tested the effect of knocking down 7SL levels in different cancer cell lines. As shown (Figure 1B), 48 h after transfecting HeLa cells (cervical carcinoma) with 7SL siRNA, 7SL levels were reduced by ∼60% compared to control cells. Silencing 7SL significantly reduced cell number in a variety of cultured cancer cell types, including HeLa cells, pancreatic carcinoma (Mia PaCa-2) and colon cancer (HCT116 and RKO) cell lines, and repressed HeLa cell growth (Figure 1C and D). Together, these data indicate that 7SL is highly expressed in cancer cells and enhanced cancer cell growth.

Bottom Line: The interaction of 7SL with TP53 mRNA reduced p53 translation, as determined by analyzing p53 expression levels, nascent p53 translation and TP53 mRNA association with polysomes.We propose that the competition between 7SL and HuR for binding to TP53 3'UTR contributes to determining the magnitude of p53 translation, in turn affecting p53 levels and the growth-suppressive function of p53.Our findings suggest that targeting 7SL may be effective in the treatment of cancers with reduced p53 levels.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA abdelmohsenk@mail.nih.gov.

Show MeSH
Related in: MedlinePlus