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LncRNA loc285194 is a p53-regulated tumor suppressor.

Liu Q, Huang J, Zhou N, Zhang Z, Zhang A, Lu Z, Wu F, Mo YY - Nucleic Acids Res. (2013)

Bottom Line: We further demonstrate a reciprocal repression between loc285194 and miR-211; in contrast to loc285194, miR-211 promotes cell growth.Finally, we detect downregulation of loc285194 in colon cancer specimens by quantitative PCR arrays and in situ hybridization of tissue microarrays.Together, these results suggest that loc285194 is a p53-regulated tumor suppressor, which acts in part through repression of miR-211.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.

ABSTRACT
Protein-coding genes account for only a small part of the human genome, whereas the vast majority of transcripts make up the non-coding RNAs including long non-coding RNAs (lncRNAs). Accumulating evidence indicates that lncRNAs could play a critical role in regulation of cellular processes such as cell growth and apoptosis as well as cancer progression and metastasis. LncRNA loc285194 was previously shown to be within a tumor suppressor unit in osteosarcoma and to suppress tumor cell growth. However, it is unknown regarding the regulation of loc285194. Moreover, the underlying mechanism by which loc285194 functions as a potential tumor suppressor is elusive. In this study, we show that loc285194 is a p53 transcription target; ectopic expression of loc285194 inhibits tumor cell growth both in vitro and in vivo. Through deletion analysis, we identify an active region responsible for tumor cell growth inhibition within exon 4, which harbors two miR-211 binding sites. Importantly, this loc285194-mediated growth inhibition is in part due to specific suppression of miR-211. We further demonstrate a reciprocal repression between loc285194 and miR-211; in contrast to loc285194, miR-211 promotes cell growth. Finally, we detect downregulation of loc285194 in colon cancer specimens by quantitative PCR arrays and in situ hybridization of tissue microarrays. Together, these results suggest that loc285194 is a p53-regulated tumor suppressor, which acts in part through repression of miR-211.

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Loc285194 is downregulated in colon cancer specimens. (A) Detection of loc285194 in TissueScan arrays by quantitative PCR. To calculate relative expression of loc285194, we took the average value of eight normal tissue samples as one and then compared each value of tumor specimens to the average value of normal tissue. Among 40 tumor samples, we only detected loc285194 expression in 38 samples; the other two were undetectable, which could be also counted as downregulation, but were not included here. (B) and (C) Detection of loc285194 in colon cancer tissue microarrays by ISH as described in ‘Materials and Methods’ section. (B) Representative pictures showing signal intensity scale: ‘0’ = negative; ‘ +’ = weak positive; ‘++’ = strong positive. (C) Loc285194 is downregulated in tumors compared with normal tissue.
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gkt182-F7: Loc285194 is downregulated in colon cancer specimens. (A) Detection of loc285194 in TissueScan arrays by quantitative PCR. To calculate relative expression of loc285194, we took the average value of eight normal tissue samples as one and then compared each value of tumor specimens to the average value of normal tissue. Among 40 tumor samples, we only detected loc285194 expression in 38 samples; the other two were undetectable, which could be also counted as downregulation, but were not included here. (B) and (C) Detection of loc285194 in colon cancer tissue microarrays by ISH as described in ‘Materials and Methods’ section. (B) Representative pictures showing signal intensity scale: ‘0’ = negative; ‘ +’ = weak positive; ‘++’ = strong positive. (C) Loc285194 is downregulated in tumors compared with normal tissue.

Mentions: In light of these findings, we then determined whether loc285194 is dysregulated in clinical specimens. We used Colon Cancer cDNA Array IV from OriGene, which contained cDNAs derived from 8 normal and 40 colon tumor specimens. The quantitative PCR analysis revealed that loc285194 was undetectable in 2 of the 40 tumor samples, which could be due to deletion of the locus. For the rest 38 tumor samples, each of them expressed loc285194 at a level lower than the average level of normal specimens, with the average expression level of 0.18 compared with normal tissue as 1 (Figure 7A).Figure 7.


LncRNA loc285194 is a p53-regulated tumor suppressor.

Liu Q, Huang J, Zhou N, Zhang Z, Zhang A, Lu Z, Wu F, Mo YY - Nucleic Acids Res. (2013)

Loc285194 is downregulated in colon cancer specimens. (A) Detection of loc285194 in TissueScan arrays by quantitative PCR. To calculate relative expression of loc285194, we took the average value of eight normal tissue samples as one and then compared each value of tumor specimens to the average value of normal tissue. Among 40 tumor samples, we only detected loc285194 expression in 38 samples; the other two were undetectable, which could be also counted as downregulation, but were not included here. (B) and (C) Detection of loc285194 in colon cancer tissue microarrays by ISH as described in ‘Materials and Methods’ section. (B) Representative pictures showing signal intensity scale: ‘0’ = negative; ‘ +’ = weak positive; ‘++’ = strong positive. (C) Loc285194 is downregulated in tumors compared with normal tissue.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643595&req=5

gkt182-F7: Loc285194 is downregulated in colon cancer specimens. (A) Detection of loc285194 in TissueScan arrays by quantitative PCR. To calculate relative expression of loc285194, we took the average value of eight normal tissue samples as one and then compared each value of tumor specimens to the average value of normal tissue. Among 40 tumor samples, we only detected loc285194 expression in 38 samples; the other two were undetectable, which could be also counted as downregulation, but were not included here. (B) and (C) Detection of loc285194 in colon cancer tissue microarrays by ISH as described in ‘Materials and Methods’ section. (B) Representative pictures showing signal intensity scale: ‘0’ = negative; ‘ +’ = weak positive; ‘++’ = strong positive. (C) Loc285194 is downregulated in tumors compared with normal tissue.
Mentions: In light of these findings, we then determined whether loc285194 is dysregulated in clinical specimens. We used Colon Cancer cDNA Array IV from OriGene, which contained cDNAs derived from 8 normal and 40 colon tumor specimens. The quantitative PCR analysis revealed that loc285194 was undetectable in 2 of the 40 tumor samples, which could be due to deletion of the locus. For the rest 38 tumor samples, each of them expressed loc285194 at a level lower than the average level of normal specimens, with the average expression level of 0.18 compared with normal tissue as 1 (Figure 7A).Figure 7.

Bottom Line: We further demonstrate a reciprocal repression between loc285194 and miR-211; in contrast to loc285194, miR-211 promotes cell growth.Finally, we detect downregulation of loc285194 in colon cancer specimens by quantitative PCR arrays and in situ hybridization of tissue microarrays.Together, these results suggest that loc285194 is a p53-regulated tumor suppressor, which acts in part through repression of miR-211.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.

ABSTRACT
Protein-coding genes account for only a small part of the human genome, whereas the vast majority of transcripts make up the non-coding RNAs including long non-coding RNAs (lncRNAs). Accumulating evidence indicates that lncRNAs could play a critical role in regulation of cellular processes such as cell growth and apoptosis as well as cancer progression and metastasis. LncRNA loc285194 was previously shown to be within a tumor suppressor unit in osteosarcoma and to suppress tumor cell growth. However, it is unknown regarding the regulation of loc285194. Moreover, the underlying mechanism by which loc285194 functions as a potential tumor suppressor is elusive. In this study, we show that loc285194 is a p53 transcription target; ectopic expression of loc285194 inhibits tumor cell growth both in vitro and in vivo. Through deletion analysis, we identify an active region responsible for tumor cell growth inhibition within exon 4, which harbors two miR-211 binding sites. Importantly, this loc285194-mediated growth inhibition is in part due to specific suppression of miR-211. We further demonstrate a reciprocal repression between loc285194 and miR-211; in contrast to loc285194, miR-211 promotes cell growth. Finally, we detect downregulation of loc285194 in colon cancer specimens by quantitative PCR arrays and in situ hybridization of tissue microarrays. Together, these results suggest that loc285194 is a p53-regulated tumor suppressor, which acts in part through repression of miR-211.

Show MeSH
Related in: MedlinePlus