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microRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and predicts favorable prognosis in gastric cancer.

Chen DL, Zhang DS, Lu YX, Chen LZ, Zeng ZL, He MM, Wang FH, Li YH, Zhang HZ, Pelicano H, Zhang W, Xu RH - Oncotarget (2015)

Bottom Line: microRNA-217 (miR-217) is frequently dysregulated in cancer.Low levels of miR-217 were associated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients.The ectopic expression of miR-217 inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas knockdown of endogenous miR-217 increased cell proliferation and invasion.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

ABSTRACT
microRNA-217 (miR-217) is frequently dysregulated in cancer. Here, we report that miR-217 levels were lower in tumor tissue compared with the adjacent normal tissue. Low levels of miR-217 were associated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients. The ectopic expression of miR-217 inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas knockdown of endogenous miR-217 increased cell proliferation and invasion. Further experiments revealed that Polycomb group protein enhancer of zeste homolog 2 (EZH2) was a direct target of miR-217 in gastric cancer cells. Knockdown of EZH2 mimicked the tumor-suppressive effects of miR-217 in gastric cancer cells, whereas the reintroduction of EZH2 abolished its effects. Taken together, these results demonstrated that miR-217 may be used as a prognostic marker, and the newly identified miR-217-EZH2 axis may be a potential target in the development of therapeutic strategies for gastric cancer patients.

No MeSH data available.


Related in: MedlinePlus

EZH2 is functional target of miR-217 in gastric cancer cells(A) and (B) Western blot and real-time PCR analysis were performed to assess the efficiency of ectopic miR-217 expression, EZH2 knockdown and EZH2 reintroduction in SGC7901 cells (*P < 0.050). (C) and (D) Colony formation and transwell assays in SGC7901 cells transfected with different plasmids.
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Figure 6: EZH2 is functional target of miR-217 in gastric cancer cells(A) and (B) Western blot and real-time PCR analysis were performed to assess the efficiency of ectopic miR-217 expression, EZH2 knockdown and EZH2 reintroduction in SGC7901 cells (*P < 0.050). (C) and (D) Colony formation and transwell assays in SGC7901 cells transfected with different plasmids.

Mentions: It has been reported that EZH2 is closely associated with tumor progression and metastasis. Considering the aforementioned results, we investigated whether miR-217 exerted its effects through the regulation of EZH2. siRNA targeting EZH2 (si-EZH2) was transfected into SGC7901 cells to knockdown endogenous EZH2 expression, and Western blot and real-time PCR analyses were performed to confirm the reduced EZH2 levels (Figure 6A and 6B). The results revealed that the knockdown of EZH2 significantly inhibited the proliferation and invasion of the SGC7901 cells, which resembled the suppressive effects of miR-217 overexpression in gastric cancer cells (Figure 6C and 6D). Moreover, the restoration of EZH2 expression in cells stably expressing miR-217 (SGC7901/miR-217) was able to counteract the inhibitory effects of miR-217 in the gastric cancer cells (Figure 6A-6D). In addition, we found that knockdown of EZH2 followed by decreasing miR-217 using miR-217 inhibitor could partially restore the EZH2 expression as well as the invasion and colony formation capacity in SGC7901 cells (Figure 7A-7D).


microRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and predicts favorable prognosis in gastric cancer.

Chen DL, Zhang DS, Lu YX, Chen LZ, Zeng ZL, He MM, Wang FH, Li YH, Zhang HZ, Pelicano H, Zhang W, Xu RH - Oncotarget (2015)

EZH2 is functional target of miR-217 in gastric cancer cells(A) and (B) Western blot and real-time PCR analysis were performed to assess the efficiency of ectopic miR-217 expression, EZH2 knockdown and EZH2 reintroduction in SGC7901 cells (*P < 0.050). (C) and (D) Colony formation and transwell assays in SGC7901 cells transfected with different plasmids.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4484425&req=5

Figure 6: EZH2 is functional target of miR-217 in gastric cancer cells(A) and (B) Western blot and real-time PCR analysis were performed to assess the efficiency of ectopic miR-217 expression, EZH2 knockdown and EZH2 reintroduction in SGC7901 cells (*P < 0.050). (C) and (D) Colony formation and transwell assays in SGC7901 cells transfected with different plasmids.
Mentions: It has been reported that EZH2 is closely associated with tumor progression and metastasis. Considering the aforementioned results, we investigated whether miR-217 exerted its effects through the regulation of EZH2. siRNA targeting EZH2 (si-EZH2) was transfected into SGC7901 cells to knockdown endogenous EZH2 expression, and Western blot and real-time PCR analyses were performed to confirm the reduced EZH2 levels (Figure 6A and 6B). The results revealed that the knockdown of EZH2 significantly inhibited the proliferation and invasion of the SGC7901 cells, which resembled the suppressive effects of miR-217 overexpression in gastric cancer cells (Figure 6C and 6D). Moreover, the restoration of EZH2 expression in cells stably expressing miR-217 (SGC7901/miR-217) was able to counteract the inhibitory effects of miR-217 in the gastric cancer cells (Figure 6A-6D). In addition, we found that knockdown of EZH2 followed by decreasing miR-217 using miR-217 inhibitor could partially restore the EZH2 expression as well as the invasion and colony formation capacity in SGC7901 cells (Figure 7A-7D).

Bottom Line: microRNA-217 (miR-217) is frequently dysregulated in cancer.Low levels of miR-217 were associated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients.The ectopic expression of miR-217 inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas knockdown of endogenous miR-217 increased cell proliferation and invasion.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

ABSTRACT
microRNA-217 (miR-217) is frequently dysregulated in cancer. Here, we report that miR-217 levels were lower in tumor tissue compared with the adjacent normal tissue. Low levels of miR-217 were associated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients. The ectopic expression of miR-217 inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas knockdown of endogenous miR-217 increased cell proliferation and invasion. Further experiments revealed that Polycomb group protein enhancer of zeste homolog 2 (EZH2) was a direct target of miR-217 in gastric cancer cells. Knockdown of EZH2 mimicked the tumor-suppressive effects of miR-217 in gastric cancer cells, whereas the reintroduction of EZH2 abolished its effects. Taken together, these results demonstrated that miR-217 may be used as a prognostic marker, and the newly identified miR-217-EZH2 axis may be a potential target in the development of therapeutic strategies for gastric cancer patients.

No MeSH data available.


Related in: MedlinePlus