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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 inhibits tumor growth in a xenograft mouse model. (A) Tumor growth curve. HCT-116 WT cells were transfected with vector or loc285194 and then injected into nude mice as described in ‘Materials and Methods’ section. Tumor growth was measured from day 7 after injection of tumor cells. Error bars represent SEM, n = 10. **P < 0.01. (B) Tumor weight when tumors were harvested. Error bars represent SEM, n = 10. *P < 0.05. (C) Total number of tumors after removal from mice.
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gkt182-F4: Loc285194 inhibits tumor growth in a xenograft mouse model. (A) Tumor growth curve. HCT-116 WT cells were transfected with vector or loc285194 and then injected into nude mice as described in ‘Materials and Methods’ section. Tumor growth was measured from day 7 after injection of tumor cells. Error bars represent SEM, n = 10. **P < 0.01. (B) Tumor weight when tumors were harvested. Error bars represent SEM, n = 10. *P < 0.05. (C) Total number of tumors after removal from mice.

Mentions: To further determine the tumor suppressive role of loc285194, we injected HCT-116 WT cells transfected with vector or loc285194 into nude mice. Compared with vector control, loc285194 significantly suppressed tumor growth based on tumor growth rate (Figure 4A) and final tumor weight (Figure 4B and C). For example, loc285294 caused >50% reduction of tumor weight compared with vector control. Therefore, loc285194 suppresses tumor cell growth not only in vitro but also in vivo, further suggesting that loc285194 is a p53 downstream effector, functioning as a tumor suppressor.Figure 4.


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 inhibits tumor growth in a xenograft mouse model. (A) Tumor growth curve. HCT-116 WT cells were transfected with vector or loc285194 and then injected into nude mice as described in ‘Materials and Methods’ section. Tumor growth was measured from day 7 after injection of tumor cells. Error bars represent SEM, n = 10. **P < 0.01. (B) Tumor weight when tumors were harvested. Error bars represent SEM, n = 10. *P < 0.05. (C) Total number of tumors after removal from mice.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gkt182-F4: Loc285194 inhibits tumor growth in a xenograft mouse model. (A) Tumor growth curve. HCT-116 WT cells were transfected with vector or loc285194 and then injected into nude mice as described in ‘Materials and Methods’ section. Tumor growth was measured from day 7 after injection of tumor cells. Error bars represent SEM, n = 10. **P < 0.01. (B) Tumor weight when tumors were harvested. Error bars represent SEM, n = 10. *P < 0.05. (C) Total number of tumors after removal from mice.
Mentions: To further determine the tumor suppressive role of loc285194, we injected HCT-116 WT cells transfected with vector or loc285194 into nude mice. Compared with vector control, loc285194 significantly suppressed tumor growth based on tumor growth rate (Figure 4A) and final tumor weight (Figure 4B and C). For example, loc285294 caused >50% reduction of tumor weight compared with vector control. Therefore, loc285194 suppresses tumor cell growth not only in vitro but also in vivo, further suggesting that loc285194 is a p53 downstream effector, functioning as a tumor suppressor.Figure 4.

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