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LncRNA NALT interaction with NOTCH1 promoted cell proliferation in pediatric T cell acute lymphoblastic leukemia.

Wang Y, Wu P, Lin R, Rong L, Xue Y, Fang Y - Sci Rep (2015)

Bottom Line: Besides, through sorting the side-population cells in T ALL cells treated with NALT shRNA could decrease percentage of SP cell which companied by the down-regulation of NOTCH1.Taken together, we found a neighbor of NOTCH1, Lnc-RP11-611D20.2 (named NALT) which could regulate the NOTCH1 signal pathway through cis-regulation.This founding may trigger a comparable development of diagnosis or novel molecularly-directed therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Nanjing Children's Hospital Affiliated with Nanjing Medical University, Nanjing 210008, China.

ABSTRACT
Long non-coding RNA (lncRNA) was referred to be participating in various malignant tumors. Location based analysis of the mechanism in lncRNA and genes have been highly focused. In this study, we reported that lncRNA named NALT which was located near NOTCH1 within 100 bp away. We confirmed that up-regulation of NALT associating with NOTCH1 in human samples. Increased expression of NALT dramatically promoted cell proliferation in cell lines via CCK8 assay and EDU stain. Further xenograft tumor also indicated the growth inducing affection of NALT while could be partial reversed by GSI. Besides, through sorting the side-population cells in T ALL cells treated with NALT shRNA could decrease percentage of SP cell which companied by the down-regulation of NOTCH1. Gal4-λN/BoxB reporter system revealed that the nuclear located NALT could function as a transcription activator which caused an activation of NOTCH signal pathway as confirmed by western blot. Taken together, we found a neighbor of NOTCH1, Lnc-RP11-611D20.2 (named NALT) which could regulate the NOTCH1 signal pathway through cis-regulation. This founding may trigger a comparable development of diagnosis or novel molecularly-directed therapies.

No MeSH data available.


Related in: MedlinePlus

NALT targeting side population cells with the interaction of NOTCH1.(A): The reduction in the SP after NALT shRNA treatment detected by flow cytometry (B): Immunocytochemistry on cytospins of sorted cells showed that all the down-regulated NOTCH1 in SP cells treated with NALT shRNA. Scale bar: 200 mm; magnification scale bars 100 mm.
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f3: NALT targeting side population cells with the interaction of NOTCH1.(A): The reduction in the SP after NALT shRNA treatment detected by flow cytometry (B): Immunocytochemistry on cytospins of sorted cells showed that all the down-regulated NOTCH1 in SP cells treated with NALT shRNA. Scale bar: 200 mm; magnification scale bars 100 mm.

Mentions: Subsequent studies have found that NOTCH signaling contributes toward the maintenance of cancer stem cells (CSCs)22. Side population (SP) cells are a rare subset of cells with a stem-like feature23. The SP phenotype has been proven to be invaluable for stem cell isolation in the absence of definitive cell surface markers24. Thus, to further investigate the function role induced by the aberrant expression level of NALT and to explore whether the interaction of NALT and NOTCH1 could affect the distribution of stem-like cells, we conducted the experiment to examine the proportion of SP cells in Jurkat cells in different groups. As a control, ABC transporter activity was inhibited using verapamil hydrochloride. In untreated samples, about 5% of SP cells were positive stained. After cells treated with NALT shRNA, less than about 1% of SP cells were detected, thus documenting that NALT might target the SP cell (Fig. 3A).


LncRNA NALT interaction with NOTCH1 promoted cell proliferation in pediatric T cell acute lymphoblastic leukemia.

Wang Y, Wu P, Lin R, Rong L, Xue Y, Fang Y - Sci Rep (2015)

NALT targeting side population cells with the interaction of NOTCH1.(A): The reduction in the SP after NALT shRNA treatment detected by flow cytometry (B): Immunocytochemistry on cytospins of sorted cells showed that all the down-regulated NOTCH1 in SP cells treated with NALT shRNA. Scale bar: 200 mm; magnification scale bars 100 mm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4557127&req=5

f3: NALT targeting side population cells with the interaction of NOTCH1.(A): The reduction in the SP after NALT shRNA treatment detected by flow cytometry (B): Immunocytochemistry on cytospins of sorted cells showed that all the down-regulated NOTCH1 in SP cells treated with NALT shRNA. Scale bar: 200 mm; magnification scale bars 100 mm.
Mentions: Subsequent studies have found that NOTCH signaling contributes toward the maintenance of cancer stem cells (CSCs)22. Side population (SP) cells are a rare subset of cells with a stem-like feature23. The SP phenotype has been proven to be invaluable for stem cell isolation in the absence of definitive cell surface markers24. Thus, to further investigate the function role induced by the aberrant expression level of NALT and to explore whether the interaction of NALT and NOTCH1 could affect the distribution of stem-like cells, we conducted the experiment to examine the proportion of SP cells in Jurkat cells in different groups. As a control, ABC transporter activity was inhibited using verapamil hydrochloride. In untreated samples, about 5% of SP cells were positive stained. After cells treated with NALT shRNA, less than about 1% of SP cells were detected, thus documenting that NALT might target the SP cell (Fig. 3A).

Bottom Line: Besides, through sorting the side-population cells in T ALL cells treated with NALT shRNA could decrease percentage of SP cell which companied by the down-regulation of NOTCH1.Taken together, we found a neighbor of NOTCH1, Lnc-RP11-611D20.2 (named NALT) which could regulate the NOTCH1 signal pathway through cis-regulation.This founding may trigger a comparable development of diagnosis or novel molecularly-directed therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Oncology, Nanjing Children's Hospital Affiliated with Nanjing Medical University, Nanjing 210008, China.

ABSTRACT
Long non-coding RNA (lncRNA) was referred to be participating in various malignant tumors. Location based analysis of the mechanism in lncRNA and genes have been highly focused. In this study, we reported that lncRNA named NALT which was located near NOTCH1 within 100 bp away. We confirmed that up-regulation of NALT associating with NOTCH1 in human samples. Increased expression of NALT dramatically promoted cell proliferation in cell lines via CCK8 assay and EDU stain. Further xenograft tumor also indicated the growth inducing affection of NALT while could be partial reversed by GSI. Besides, through sorting the side-population cells in T ALL cells treated with NALT shRNA could decrease percentage of SP cell which companied by the down-regulation of NOTCH1. Gal4-λN/BoxB reporter system revealed that the nuclear located NALT could function as a transcription activator which caused an activation of NOTCH signal pathway as confirmed by western blot. Taken together, we found a neighbor of NOTCH1, Lnc-RP11-611D20.2 (named NALT) which could regulate the NOTCH1 signal pathway through cis-regulation. This founding may trigger a comparable development of diagnosis or novel molecularly-directed therapies.

No MeSH data available.


Related in: MedlinePlus