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miR-512-5p suppresses tumor growth by targeting hTERT in telomerase positive head and neck squamous cell carcinoma in vitro and in vivo.

Li J, Lei H, Xu Y, Tao ZZ - PLoS ONE (2015)

Bottom Line: Both in vitro and in vivo assays revealed that miR-512-5P mimic attenuated HNSCC cell proliferation, and tumor growth in nude mice, which exerts its tumor suppressor function through elevated apoptosis, inhibition of the telomerase activity, decrease of telomere-binding proteins and shortening of telomere length by human telomerase reverse transcriptase (hTERT) downregulation.We conclude that the frequently miR-512-5P overexpression can regulate hTERT and function as a tumor suppressor in HNSCC.Therefore, miR-512-5P may serve as a potential therapeutic agent for miR-based HNSCC therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

ABSTRACT
Telomerase activation has very important implications for head and neck squamous cell carcinoma (HNSCC), but the regulatory mechanisms of telomerase in HNSCC remain unclear. In our present study, we found that miR-512-5P was markedly downregulated in telomerase-positive HNSCC cell lines. Both in vitro and in vivo assays revealed that miR-512-5P mimic attenuated HNSCC cell proliferation, and tumor growth in nude mice, which exerts its tumor suppressor function through elevated apoptosis, inhibition of the telomerase activity, decrease of telomere-binding proteins and shortening of telomere length by human telomerase reverse transcriptase (hTERT) downregulation. Furthermore, the dual-luciferase reporter gene assay results demonstrated that hTERT was a direct target of miR-512-5P. We conclude that the frequently miR-512-5P overexpression can regulate hTERT and function as a tumor suppressor in HNSCC. Therefore, miR-512-5P may serve as a potential therapeutic agent for miR-based HNSCC therapy.

No MeSH data available.


Related in: MedlinePlus

MiR-512-5p is down-regulated in in telomerase positive HNSCC cell lines.(A) MicroRNA array indicated that miR-512-5P was the most dramatically decreased among the miRs with significantly changed expression levels in telometase positive cell lines. (B) qRT-PCR analysis of the expression levels of miR-512-5p in various telomerase status cell lines. All data are shown as mean±SD. *P<0.05.
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pone.0135265.g001: MiR-512-5p is down-regulated in in telomerase positive HNSCC cell lines.(A) MicroRNA array indicated that miR-512-5P was the most dramatically decreased among the miRs with significantly changed expression levels in telometase positive cell lines. (B) qRT-PCR analysis of the expression levels of miR-512-5p in various telomerase status cell lines. All data are shown as mean±SD. *P<0.05.

Mentions: To determine the role of miRs in telomerase regulation, two telomerase positive cell lines (Hep-2, CNE) and two telomerase negative cell lines (BEAS-2B, U-2 OS) were assembled for microRNA profiling analysis. In telomerase positive cell lines7 miRs were down-regulated and 5 miRs were up-regulated compared to telomerase negative ones (Fig 1A and Table 1). Among the miRs with significantly changed expression levels, miR-512-5P was the most dramatically decreased by 0.13-fold (p<0.01). Consistent with the microRNA array results, QRT-PCR further validates that miR-512-5p levels were down-regulated in telomerase positive cell lines (Fig 1B). These findings suggested that miR-512-5p was reduced in telomerase positive HNSCC cell lines.


miR-512-5p suppresses tumor growth by targeting hTERT in telomerase positive head and neck squamous cell carcinoma in vitro and in vivo.

Li J, Lei H, Xu Y, Tao ZZ - PLoS ONE (2015)

MiR-512-5p is down-regulated in in telomerase positive HNSCC cell lines.(A) MicroRNA array indicated that miR-512-5P was the most dramatically decreased among the miRs with significantly changed expression levels in telometase positive cell lines. (B) qRT-PCR analysis of the expression levels of miR-512-5p in various telomerase status cell lines. All data are shown as mean±SD. *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530866&req=5

pone.0135265.g001: MiR-512-5p is down-regulated in in telomerase positive HNSCC cell lines.(A) MicroRNA array indicated that miR-512-5P was the most dramatically decreased among the miRs with significantly changed expression levels in telometase positive cell lines. (B) qRT-PCR analysis of the expression levels of miR-512-5p in various telomerase status cell lines. All data are shown as mean±SD. *P<0.05.
Mentions: To determine the role of miRs in telomerase regulation, two telomerase positive cell lines (Hep-2, CNE) and two telomerase negative cell lines (BEAS-2B, U-2 OS) were assembled for microRNA profiling analysis. In telomerase positive cell lines7 miRs were down-regulated and 5 miRs were up-regulated compared to telomerase negative ones (Fig 1A and Table 1). Among the miRs with significantly changed expression levels, miR-512-5P was the most dramatically decreased by 0.13-fold (p<0.01). Consistent with the microRNA array results, QRT-PCR further validates that miR-512-5p levels were down-regulated in telomerase positive cell lines (Fig 1B). These findings suggested that miR-512-5p was reduced in telomerase positive HNSCC cell lines.

Bottom Line: Both in vitro and in vivo assays revealed that miR-512-5P mimic attenuated HNSCC cell proliferation, and tumor growth in nude mice, which exerts its tumor suppressor function through elevated apoptosis, inhibition of the telomerase activity, decrease of telomere-binding proteins and shortening of telomere length by human telomerase reverse transcriptase (hTERT) downregulation.We conclude that the frequently miR-512-5P overexpression can regulate hTERT and function as a tumor suppressor in HNSCC.Therefore, miR-512-5P may serve as a potential therapeutic agent for miR-based HNSCC therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

ABSTRACT
Telomerase activation has very important implications for head and neck squamous cell carcinoma (HNSCC), but the regulatory mechanisms of telomerase in HNSCC remain unclear. In our present study, we found that miR-512-5P was markedly downregulated in telomerase-positive HNSCC cell lines. Both in vitro and in vivo assays revealed that miR-512-5P mimic attenuated HNSCC cell proliferation, and tumor growth in nude mice, which exerts its tumor suppressor function through elevated apoptosis, inhibition of the telomerase activity, decrease of telomere-binding proteins and shortening of telomere length by human telomerase reverse transcriptase (hTERT) downregulation. Furthermore, the dual-luciferase reporter gene assay results demonstrated that hTERT was a direct target of miR-512-5P. We conclude that the frequently miR-512-5P overexpression can regulate hTERT and function as a tumor suppressor in HNSCC. Therefore, miR-512-5P may serve as a potential therapeutic agent for miR-based HNSCC therapy.

No MeSH data available.


Related in: MedlinePlus