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miR-98 targets ITGB3 to inhibit proliferation, migration, and invasion of non-small-cell lung cancer.

Ni R, Huang Y, Wang J - Onco Targets Ther (2015)

Bottom Line: Finally, we transplanted miR-98 expressing A549 cells into nude mice to observe the effect of miR-98 on tumor growth in vivo.Furthermore, we identified that miR-98 exerted inhibitory roles by directly binding to 3'-UTR of ITGB3 mRNA, thus negatively regulated the expression of ITGB3.Interestingly, upon restoring the expression of ITGB3, the effect of miR-98 on cell proliferation was partially reversed.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiration Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

ABSTRACT

Background: Accumulating evidence has emphasized causative links between aberrant microRNA (miR) expression patterns and cancer development. Abnormally expressed miRNA-98 (miR-98) was found in certain types of human cancers. The biological roles of miR-98 in lung cancer, however, remain largely undefined.

Methods: We evaluated the expression of miR-98 in normal lung tissues, lung cancer tissues, normal human bronchial epithelial cells, and lung cancer cells using quantitative real-time polymerase chain reaction. Effect of miR-98 on proliferation of lung cancer cells was investigated using MTT assay and colony formation assay. Transwell assay was used to assess the effects of miR-98 on migration and invasion of lung cancer cells. Whether miR-98 targets the 3'-untranslated region (3'-UTR) of integrin β3 (ITGB3) coding gene ITGB3 mRNA was ascertained using luciferase reporter assay. Finally, we transplanted miR-98 expressing A549 cells into nude mice to observe the effect of miR-98 on tumor growth in vivo.

Results: We confirmed that miR-98 was frequently low expressed in lung cancer tissues and human lung cancer cells. Reintroduction of miR-98 into lung cancer cells inhibited cell proliferation, migration, and invasion in vitro and suppressed tumor formation in a nude mouse model. Furthermore, we identified that miR-98 exerted inhibitory roles by directly binding to 3'-UTR of ITGB3 mRNA, thus negatively regulated the expression of ITGB3. Interestingly, upon restoring the expression of ITGB3, the effect of miR-98 on cell proliferation was partially reversed.

Conclusion: Our findings suggest that miR-98 prevents proliferation, migration, and invasion of lung cancer cells by directly binding to the 3'-UTR of ITGB3 mRNA and could be a promising treatment option in anticancer therapy.

No MeSH data available.


Related in: MedlinePlus

miR-98 is low expressed in lung cancer, and restoration of miR-98 inhibits cell proliferation.Notes: (A) miR-98 is downregulated in lung cancer tissues. **P<0.01 vs normal tissues. (B) miR-98 is downregulated in lung cancer cells. *P<0.05. **P<0.01 vs normal HBE cells. (C) Relative miR-98 level is elevated in PC9 and A549 cells transfected with miR-98 mimics. ***P<0.001 vs controls. (D and E) miR-98 inhibits absorbance of PC9 and A549 cells, respectively. *P<0.05 vs controls. (F) miR-98 suppresses the colony formation abilities of PC9 and A549 cells.Abbreviations: HBE, human bronchial epithelial; d, days.
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f1-ott-8-2689: miR-98 is low expressed in lung cancer, and restoration of miR-98 inhibits cell proliferation.Notes: (A) miR-98 is downregulated in lung cancer tissues. **P<0.01 vs normal tissues. (B) miR-98 is downregulated in lung cancer cells. *P<0.05. **P<0.01 vs normal HBE cells. (C) Relative miR-98 level is elevated in PC9 and A549 cells transfected with miR-98 mimics. ***P<0.001 vs controls. (D and E) miR-98 inhibits absorbance of PC9 and A549 cells, respectively. *P<0.05 vs controls. (F) miR-98 suppresses the colony formation abilities of PC9 and A549 cells.Abbreviations: HBE, human bronchial epithelial; d, days.

Mentions: Table 1 shows a summary of patient characteristics and some pathological features. Median age was 62 years (range, 45–77) and 61.5% were males. Fifteen (57.7%) patients had smoking history. Eight (44.4%) patients had stage I disease and 18 stage II. Twenty-two (84.6%) patients had adenocarcinoma and four (15.4%) large cell carcinoma. One metastatic site was found in eleven patients (42.3%) and over two metastatic sites in seven patients (26.9%). According to the quantitative real-time polymerase chain reaction result, the relative expression level of miR-98 in different lung cancer tissues and cells are shown in Figure 1A and B. Compared to normal tissues, miR-98 was significantly downregulated in lung cancer tissues, with a ratio of 0.27±0.08 vs 1.0±0.02. Besides, the expression of miR-98 was also downregulated in A549, SKMES-1, PC9, H1650, HCC827, and NCL-H358 lung cells, with the corresponding values of relative expression 0.24±0.08, 0.31±0.07, 0.45±0.08, 0.52±0.12, 0.53±0.11, and 0.65±0.09, respectively.


miR-98 targets ITGB3 to inhibit proliferation, migration, and invasion of non-small-cell lung cancer.

Ni R, Huang Y, Wang J - Onco Targets Ther (2015)

miR-98 is low expressed in lung cancer, and restoration of miR-98 inhibits cell proliferation.Notes: (A) miR-98 is downregulated in lung cancer tissues. **P<0.01 vs normal tissues. (B) miR-98 is downregulated in lung cancer cells. *P<0.05. **P<0.01 vs normal HBE cells. (C) Relative miR-98 level is elevated in PC9 and A549 cells transfected with miR-98 mimics. ***P<0.001 vs controls. (D and E) miR-98 inhibits absorbance of PC9 and A549 cells, respectively. *P<0.05 vs controls. (F) miR-98 suppresses the colony formation abilities of PC9 and A549 cells.Abbreviations: HBE, human bronchial epithelial; d, days.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4590683&req=5

f1-ott-8-2689: miR-98 is low expressed in lung cancer, and restoration of miR-98 inhibits cell proliferation.Notes: (A) miR-98 is downregulated in lung cancer tissues. **P<0.01 vs normal tissues. (B) miR-98 is downregulated in lung cancer cells. *P<0.05. **P<0.01 vs normal HBE cells. (C) Relative miR-98 level is elevated in PC9 and A549 cells transfected with miR-98 mimics. ***P<0.001 vs controls. (D and E) miR-98 inhibits absorbance of PC9 and A549 cells, respectively. *P<0.05 vs controls. (F) miR-98 suppresses the colony formation abilities of PC9 and A549 cells.Abbreviations: HBE, human bronchial epithelial; d, days.
Mentions: Table 1 shows a summary of patient characteristics and some pathological features. Median age was 62 years (range, 45–77) and 61.5% were males. Fifteen (57.7%) patients had smoking history. Eight (44.4%) patients had stage I disease and 18 stage II. Twenty-two (84.6%) patients had adenocarcinoma and four (15.4%) large cell carcinoma. One metastatic site was found in eleven patients (42.3%) and over two metastatic sites in seven patients (26.9%). According to the quantitative real-time polymerase chain reaction result, the relative expression level of miR-98 in different lung cancer tissues and cells are shown in Figure 1A and B. Compared to normal tissues, miR-98 was significantly downregulated in lung cancer tissues, with a ratio of 0.27±0.08 vs 1.0±0.02. Besides, the expression of miR-98 was also downregulated in A549, SKMES-1, PC9, H1650, HCC827, and NCL-H358 lung cells, with the corresponding values of relative expression 0.24±0.08, 0.31±0.07, 0.45±0.08, 0.52±0.12, 0.53±0.11, and 0.65±0.09, respectively.

Bottom Line: Finally, we transplanted miR-98 expressing A549 cells into nude mice to observe the effect of miR-98 on tumor growth in vivo.Furthermore, we identified that miR-98 exerted inhibitory roles by directly binding to 3'-UTR of ITGB3 mRNA, thus negatively regulated the expression of ITGB3.Interestingly, upon restoring the expression of ITGB3, the effect of miR-98 on cell proliferation was partially reversed.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiration Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

ABSTRACT

Background: Accumulating evidence has emphasized causative links between aberrant microRNA (miR) expression patterns and cancer development. Abnormally expressed miRNA-98 (miR-98) was found in certain types of human cancers. The biological roles of miR-98 in lung cancer, however, remain largely undefined.

Methods: We evaluated the expression of miR-98 in normal lung tissues, lung cancer tissues, normal human bronchial epithelial cells, and lung cancer cells using quantitative real-time polymerase chain reaction. Effect of miR-98 on proliferation of lung cancer cells was investigated using MTT assay and colony formation assay. Transwell assay was used to assess the effects of miR-98 on migration and invasion of lung cancer cells. Whether miR-98 targets the 3'-untranslated region (3'-UTR) of integrin β3 (ITGB3) coding gene ITGB3 mRNA was ascertained using luciferase reporter assay. Finally, we transplanted miR-98 expressing A549 cells into nude mice to observe the effect of miR-98 on tumor growth in vivo.

Results: We confirmed that miR-98 was frequently low expressed in lung cancer tissues and human lung cancer cells. Reintroduction of miR-98 into lung cancer cells inhibited cell proliferation, migration, and invasion in vitro and suppressed tumor formation in a nude mouse model. Furthermore, we identified that miR-98 exerted inhibitory roles by directly binding to 3'-UTR of ITGB3 mRNA, thus negatively regulated the expression of ITGB3. Interestingly, upon restoring the expression of ITGB3, the effect of miR-98 on cell proliferation was partially reversed.

Conclusion: Our findings suggest that miR-98 prevents proliferation, migration, and invasion of lung cancer cells by directly binding to the 3'-UTR of ITGB3 mRNA and could be a promising treatment option in anticancer therapy.

No MeSH data available.


Related in: MedlinePlus