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miR-26a suppresses tumor growth and metastasis by targeting FGF9 in gastric cancer.

Deng M, Tang HL, Lu XH, Liu MY, Lu XM, Gu YX, Liu JF, He ZM - PLoS ONE (2013)

Bottom Line: In this study, we found that miR-26a was strongly downregulated in gastric cancer (GC) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of GC.We also found that ectopic expression of miR-26a inhibited GC cell proliferation and GC metastasis in vitro and in vivo.In addition, miR-26a expression inversely correlated with FGF9 protein levels in GC.

View Article: PubMed Central - PubMed

Affiliation: Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou, China ; Cancer Research Institute, University of South China, Hengyang, China.

ABSTRACT
The role of miR-26a in cancer cells seemed controversial in previous studies. Until now, the role of miR-26a in gastric cancer remains undefined. In this study, we found that miR-26a was strongly downregulated in gastric cancer (GC) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of GC. We also found that ectopic expression of miR-26a inhibited GC cell proliferation and GC metastasis in vitro and in vivo. We further identified a novel mechanism of miR-26a to suppress GC growth and metastasis. FGF9 was proved to be a direct target of miR-26a, using luciferase assay and western blot. FGF9 overexpression in miR-26a-expressing cells could rescue invasion and growth defects of miR-26a. In addition, miR-26a expression inversely correlated with FGF9 protein levels in GC. Taken together, our data suggest that miR-26a functions as a tumor suppressor in GC development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for GC.

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miR-26a inhibits cell migration, invasion, growth and soft agar colony formation, and induces cell apoptosis in GC.(A, B) The wound healing assay (A) and invasion assay (B) of SGC-7901 and AGS cells infected with miR-26a or scramble lentivirus. The invasion assay was measured by way of Transwell assays with Matrigel. (C) The growth of SGC-7901 and AGS cells infected with miR-26a or scramble lentivirus was assayed. (D) Colony growth assays in soft agar were performed on SGC-7901 with overexpression of miR-26a or scramble. Representative images of the assays are shown (left panel). Original magnification: ×200. (E) Overexpression of miR-26a induces tumor cell apoptosis. SGC-7901 cells were infected with miR-26a or scramble lentivirus. The apoptotic cells were evaluated by Annexin V-FITC and propidium iodine staining and analyzed with FACS. All data are presented.as mean ± s.e.m from at least three separate experiments.
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pone-0072662-g002: miR-26a inhibits cell migration, invasion, growth and soft agar colony formation, and induces cell apoptosis in GC.(A, B) The wound healing assay (A) and invasion assay (B) of SGC-7901 and AGS cells infected with miR-26a or scramble lentivirus. The invasion assay was measured by way of Transwell assays with Matrigel. (C) The growth of SGC-7901 and AGS cells infected with miR-26a or scramble lentivirus was assayed. (D) Colony growth assays in soft agar were performed on SGC-7901 with overexpression of miR-26a or scramble. Representative images of the assays are shown (left panel). Original magnification: ×200. (E) Overexpression of miR-26a induces tumor cell apoptosis. SGC-7901 cells were infected with miR-26a or scramble lentivirus. The apoptotic cells were evaluated by Annexin V-FITC and propidium iodine staining and analyzed with FACS. All data are presented.as mean ± s.e.m from at least three separate experiments.

Mentions: Noting the inverse correlation between miR-26a levels and metastasis, we investigated the effect of miR-26a re-expression on the migration and invasion abilities of GC cell lines. Two GC cell lines (SGC-7901 and AGS) with relatively low basal expression of miR-26a (Figure 1B) were infected with either miR-26a or control lentivirus and selected with 5 mg/l puromycin for two weeks. Next, wound healing assay and transwell assay were performed. As expected, overexpression of miR-26a significantly suppressed cell migration and invasion abilities (Figure 2A, B; Figure S1).


miR-26a suppresses tumor growth and metastasis by targeting FGF9 in gastric cancer.

Deng M, Tang HL, Lu XH, Liu MY, Lu XM, Gu YX, Liu JF, He ZM - PLoS ONE (2013)

miR-26a inhibits cell migration, invasion, growth and soft agar colony formation, and induces cell apoptosis in GC.(A, B) The wound healing assay (A) and invasion assay (B) of SGC-7901 and AGS cells infected with miR-26a or scramble lentivirus. The invasion assay was measured by way of Transwell assays with Matrigel. (C) The growth of SGC-7901 and AGS cells infected with miR-26a or scramble lentivirus was assayed. (D) Colony growth assays in soft agar were performed on SGC-7901 with overexpression of miR-26a or scramble. Representative images of the assays are shown (left panel). Original magnification: ×200. (E) Overexpression of miR-26a induces tumor cell apoptosis. SGC-7901 cells were infected with miR-26a or scramble lentivirus. The apoptotic cells were evaluated by Annexin V-FITC and propidium iodine staining and analyzed with FACS. All data are presented.as mean ± s.e.m from at least three separate experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756000&req=5

pone-0072662-g002: miR-26a inhibits cell migration, invasion, growth and soft agar colony formation, and induces cell apoptosis in GC.(A, B) The wound healing assay (A) and invasion assay (B) of SGC-7901 and AGS cells infected with miR-26a or scramble lentivirus. The invasion assay was measured by way of Transwell assays with Matrigel. (C) The growth of SGC-7901 and AGS cells infected with miR-26a or scramble lentivirus was assayed. (D) Colony growth assays in soft agar were performed on SGC-7901 with overexpression of miR-26a or scramble. Representative images of the assays are shown (left panel). Original magnification: ×200. (E) Overexpression of miR-26a induces tumor cell apoptosis. SGC-7901 cells were infected with miR-26a or scramble lentivirus. The apoptotic cells were evaluated by Annexin V-FITC and propidium iodine staining and analyzed with FACS. All data are presented.as mean ± s.e.m from at least three separate experiments.
Mentions: Noting the inverse correlation between miR-26a levels and metastasis, we investigated the effect of miR-26a re-expression on the migration and invasion abilities of GC cell lines. Two GC cell lines (SGC-7901 and AGS) with relatively low basal expression of miR-26a (Figure 1B) were infected with either miR-26a or control lentivirus and selected with 5 mg/l puromycin for two weeks. Next, wound healing assay and transwell assay were performed. As expected, overexpression of miR-26a significantly suppressed cell migration and invasion abilities (Figure 2A, B; Figure S1).

Bottom Line: In this study, we found that miR-26a was strongly downregulated in gastric cancer (GC) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of GC.We also found that ectopic expression of miR-26a inhibited GC cell proliferation and GC metastasis in vitro and in vivo.In addition, miR-26a expression inversely correlated with FGF9 protein levels in GC.

View Article: PubMed Central - PubMed

Affiliation: Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou, China ; Cancer Research Institute, University of South China, Hengyang, China.

ABSTRACT
The role of miR-26a in cancer cells seemed controversial in previous studies. Until now, the role of miR-26a in gastric cancer remains undefined. In this study, we found that miR-26a was strongly downregulated in gastric cancer (GC) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of GC. We also found that ectopic expression of miR-26a inhibited GC cell proliferation and GC metastasis in vitro and in vivo. We further identified a novel mechanism of miR-26a to suppress GC growth and metastasis. FGF9 was proved to be a direct target of miR-26a, using luciferase assay and western blot. FGF9 overexpression in miR-26a-expressing cells could rescue invasion and growth defects of miR-26a. In addition, miR-26a expression inversely correlated with FGF9 protein levels in GC. Taken together, our data suggest that miR-26a functions as a tumor suppressor in GC development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for GC.

Show MeSH
Related in: MedlinePlus