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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

The effect of miR-512-5p on CNE cell growth, apoptosis and telomere maintenance.(A) MTT assay showed that overexpression of miR-512-5p in CNE cells resulted in inhibition of cell growth in vitro. (B) Forty-eight hours post-transfection,apoptosis was determined by flow cytometric detection of Annexin-V-FITC-positive/PI-negative cells. (C) One day post-transfection, a remarkable inhibition of telomerase activity was observed in cells transfected with miR-512-5P mimic in comparison with the cells transfected with scramble. (D) Four days post-transfection, miR-512-5p mimic groups showed a significant decrease in relative telomere length. All data are shown as mean±SD of triplicate experiments. *P<0.05.
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pone.0135265.g002: The effect of miR-512-5p on CNE cell growth, apoptosis and telomere maintenance.(A) MTT assay showed that overexpression of miR-512-5p in CNE cells resulted in inhibition of cell growth in vitro. (B) Forty-eight hours post-transfection,apoptosis was determined by flow cytometric detection of Annexin-V-FITC-positive/PI-negative cells. (C) One day post-transfection, a remarkable inhibition of telomerase activity was observed in cells transfected with miR-512-5P mimic in comparison with the cells transfected with scramble. (D) Four days post-transfection, miR-512-5p mimic groups showed a significant decrease in relative telomere length. All data are shown as mean±SD of triplicate experiments. *P<0.05.

Mentions: In order to better characterize the impact of miR-512-5P on cancer cell proliferation, we introduced miR-512-5P mimics into the CNE cells. The transduction of miR-512-5P mimic showed a significant inhibition of cell proliferation in CNE cells, in comparison with those transduced with scramble as determined by MTT assay (Fig 2A). Furthermore, we observed that apoptosis rate weas significantly increased in miR-512-5P mimics-treated cells (Fig 2B). The results showed that up-regulation of miR-512-5P led to remarkable inhibition of cell proliferation and significantly increased apoptosis in HNSCC cells.


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)

The effect of miR-512-5p on CNE cell growth, apoptosis and telomere maintenance.(A) MTT assay showed that overexpression of miR-512-5p in CNE cells resulted in inhibition of cell growth in vitro. (B) Forty-eight hours post-transfection,apoptosis was determined by flow cytometric detection of Annexin-V-FITC-positive/PI-negative cells. (C) One day post-transfection, a remarkable inhibition of telomerase activity was observed in cells transfected with miR-512-5P mimic in comparison with the cells transfected with scramble. (D) Four days post-transfection, miR-512-5p mimic groups showed a significant decrease in relative telomere length. All data are shown as mean±SD of triplicate experiments. *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135265.g002: The effect of miR-512-5p on CNE cell growth, apoptosis and telomere maintenance.(A) MTT assay showed that overexpression of miR-512-5p in CNE cells resulted in inhibition of cell growth in vitro. (B) Forty-eight hours post-transfection,apoptosis was determined by flow cytometric detection of Annexin-V-FITC-positive/PI-negative cells. (C) One day post-transfection, a remarkable inhibition of telomerase activity was observed in cells transfected with miR-512-5P mimic in comparison with the cells transfected with scramble. (D) Four days post-transfection, miR-512-5p mimic groups showed a significant decrease in relative telomere length. All data are shown as mean±SD of triplicate experiments. *P<0.05.
Mentions: In order to better characterize the impact of miR-512-5P on cancer cell proliferation, we introduced miR-512-5P mimics into the CNE cells. The transduction of miR-512-5P mimic showed a significant inhibition of cell proliferation in CNE cells, in comparison with those transduced with scramble as determined by MTT assay (Fig 2A). Furthermore, we observed that apoptosis rate weas significantly increased in miR-512-5P mimics-treated cells (Fig 2B). The results showed that up-regulation of miR-512-5P led to remarkable inhibition of cell proliferation and significantly increased apoptosis in HNSCC cells.

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