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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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miR-211 promotes cell growth in HCT-116 WT (A) and MCF-7 cells (B). Cells were transfected with vector or miR-211 overnight, and then split into 12-well plates. Cell number was countered from day 1 (as 100%) to day 4. Error bars represent SEM, n = 3. **P < 0.01; *P < 0.05.
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gkt182-F6: miR-211 promotes cell growth in HCT-116 WT (A) and MCF-7 cells (B). Cells were transfected with vector or miR-211 overnight, and then split into 12-well plates. Cell number was countered from day 1 (as 100%) to day 4. Error bars represent SEM, n = 3. **P < 0.01; *P < 0.05.

Mentions: The role of miR-211 in cancer appears to be cell-type specific. In melanoma, miR-211 was reported to function as a tumor suppressor (33). However, in other types of cancers such as colon and oral cancers, miR-211 may function as an oncogene (34,35) because ectopic expression of miR-211 promotes cell growth. Therefore, we asked whether ectopic expression of miR-211 (Supplementary Figure S7) promotes cell growth in colon cancer HCT-116 cells. As expected, miR-211 significantly increased cell growth in HCT-116 WT cells (Figure 6A). This miR-211-promoted cell growth was also seen in breast cancer MCF-7 cells (Figure 6B), suggesting that loc285194 inhibits tumor cell growth in part through negative regulation of miR-211.Figure 6.


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)

miR-211 promotes cell growth in HCT-116 WT (A) and MCF-7 cells (B). Cells were transfected with vector or miR-211 overnight, and then split into 12-well plates. Cell number was countered from day 1 (as 100%) to day 4. Error bars represent SEM, n = 3. **P < 0.01; *P < 0.05.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gkt182-F6: miR-211 promotes cell growth in HCT-116 WT (A) and MCF-7 cells (B). Cells were transfected with vector or miR-211 overnight, and then split into 12-well plates. Cell number was countered from day 1 (as 100%) to day 4. Error bars represent SEM, n = 3. **P < 0.01; *P < 0.05.
Mentions: The role of miR-211 in cancer appears to be cell-type specific. In melanoma, miR-211 was reported to function as a tumor suppressor (33). However, in other types of cancers such as colon and oral cancers, miR-211 may function as an oncogene (34,35) because ectopic expression of miR-211 promotes cell growth. Therefore, we asked whether ectopic expression of miR-211 (Supplementary Figure S7) promotes cell growth in colon cancer HCT-116 cells. As expected, miR-211 significantly increased cell growth in HCT-116 WT cells (Figure 6A). This miR-211-promoted cell growth was also seen in breast cancer MCF-7 cells (Figure 6B), suggesting that loc285194 inhibits tumor cell growth in part through negative regulation of miR-211.Figure 6.

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