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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

In vivo effect of miR-512-5p on CNE cell growth in nude mice. Tumor size was measured weekly using method mentioned above.(A) Growth curves for CNE/miR-512-5p mimic (n = 10) or CNE/scramble (n = 10) cells by in vivo proliferation assay. (B) Tumors were weighed after animals were killed at 5 weeks after injection. The weight of tumors was significantly decreased in miR-512-5p group compared to scramble group (p = 0.009). (C) Representative photomicrographs of immunohistochemical staining of TERT on xenograft tumor sections obtained from mice in miR-512-5p and scramble groups by immunohistochemistry at 400× magnifications. All data are shown as mean±SD. *P<0.05.
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pone.0135265.g004: In vivo effect of miR-512-5p on CNE cell growth in nude mice. Tumor size was measured weekly using method mentioned above.(A) Growth curves for CNE/miR-512-5p mimic (n = 10) or CNE/scramble (n = 10) cells by in vivo proliferation assay. (B) Tumors were weighed after animals were killed at 5 weeks after injection. The weight of tumors was significantly decreased in miR-512-5p group compared to scramble group (p = 0.009). (C) Representative photomicrographs of immunohistochemical staining of TERT on xenograft tumor sections obtained from mice in miR-512-5p and scramble groups by immunohistochemistry at 400× magnifications. All data are shown as mean±SD. *P<0.05.

Mentions: To investigate the in vivo effect of miR-512-5p, equal numbers of CNE cells treated with miR-512-5p or the scramble were subcutaneously injected into nude mice and immunohistochemistry assays for hTERT were performed. Data of tumor volume (Fig 4A) showed that CNE cells treated with scramble led to larger tumors more rapidly than miR-512-5p-transfected cells in nude mice(P<0.01). Similarly, compared to the scramble group (3.81±0.87 g), mice injected with miR-512-5p mimic transfected cells (1.23±0.35 g) showed a significant decrease in tumor weight (Fig 4B). Furthermore, the expression of hTERT protein was dramatically down-regulated in the miR-512-5p treatment group compared with the scramble group (Fig 4C). These results demonstrated that miR-512-5p suppresses tumor growth and hTERT protein expression in vivo.


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)

In vivo effect of miR-512-5p on CNE cell growth in nude mice. Tumor size was measured weekly using method mentioned above.(A) Growth curves for CNE/miR-512-5p mimic (n = 10) or CNE/scramble (n = 10) cells by in vivo proliferation assay. (B) Tumors were weighed after animals were killed at 5 weeks after injection. The weight of tumors was significantly decreased in miR-512-5p group compared to scramble group (p = 0.009). (C) Representative photomicrographs of immunohistochemical staining of TERT on xenograft tumor sections obtained from mice in miR-512-5p and scramble groups by immunohistochemistry at 400× magnifications. All data are shown as mean±SD. *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135265.g004: In vivo effect of miR-512-5p on CNE cell growth in nude mice. Tumor size was measured weekly using method mentioned above.(A) Growth curves for CNE/miR-512-5p mimic (n = 10) or CNE/scramble (n = 10) cells by in vivo proliferation assay. (B) Tumors were weighed after animals were killed at 5 weeks after injection. The weight of tumors was significantly decreased in miR-512-5p group compared to scramble group (p = 0.009). (C) Representative photomicrographs of immunohistochemical staining of TERT on xenograft tumor sections obtained from mice in miR-512-5p and scramble groups by immunohistochemistry at 400× magnifications. All data are shown as mean±SD. *P<0.05.
Mentions: To investigate the in vivo effect of miR-512-5p, equal numbers of CNE cells treated with miR-512-5p or the scramble were subcutaneously injected into nude mice and immunohistochemistry assays for hTERT were performed. Data of tumor volume (Fig 4A) showed that CNE cells treated with scramble led to larger tumors more rapidly than miR-512-5p-transfected cells in nude mice(P<0.01). Similarly, compared to the scramble group (3.81±0.87 g), mice injected with miR-512-5p mimic transfected cells (1.23±0.35 g) showed a significant decrease in tumor weight (Fig 4B). Furthermore, the expression of hTERT protein was dramatically down-regulated in the miR-512-5p treatment group compared with the scramble group (Fig 4C). These results demonstrated that miR-512-5p suppresses tumor growth and hTERT protein expression in vivo.

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