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MiR-26a inhibits proliferation and migration of breast cancer through repression of MCL-1.

Gao J, Li L, Wu M, Liu M, Xie X, Guo J, Tang H, Xie X - PLoS ONE (2013)

Bottom Line: MicroRNAs are a family of small non-coding RNAs 18-25 nucleotides in length that post-transcriptionally modulate gene expression.MCL-1, an anti-apoptotic member of the Bcl-2 family, as novel targets of miR-26a was found to be in reverse correlation with ectopic expression of miR-26a and knockdown of MCL-1 phenocopied the effect of miR-26a in breast cancer cell lines.Thus, miR-26a impacts on cell proliferation and migration of breast cancer by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of MCL-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.

ABSTRACT
Breast cancer is the most commonly malignancies in women. MicroRNAs are a family of small non-coding RNAs 18-25 nucleotides in length that post-transcriptionally modulate gene expression. MiR-26a has been reported as a tumor suppressor microRNA in breast cancer, which is attributed mainly to targeting of MTDH and EZH2, however, the expression profile and therapeutic potential of miR-26a is still unclear. Here we demonstrate that miR-26a is down-regulated in breast cancer cells and clinical specimens and its modulation in breast cancer cells regulates cell proliferation, colony formation, migration and apoptosis. MCL-1, an anti-apoptotic member of the Bcl-2 family, as novel targets of miR-26a was found to be in reverse correlation with ectopic expression of miR-26a and knockdown of MCL-1 phenocopied the effect of miR-26a in breast cancer cell lines. It was further explored that miR-26a increased sensitivity of breast cancer cells to paclitaxel in which MCL-1 was involved. Thus, miR-26a impacts on cell proliferation and migration of breast cancer by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of MCL-1.

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Related in: MedlinePlus

Knockdown of MCL-1 suppresses cell proliferation, clonogenicity and induces cell apoptosis.A. Does effect and time effect of transfection of MCL-1-siRNA on the proliferation of MDA-MB-231 and MCF-7 cells. B. The functional role of MCL-1 in breast cancer cell growth was analyzed by colony formation of MDA-MB-231 and MCF-7 cells. The evaluation of colony numbers was shown in the panel. C. Influence of MCL-1 on apoptosis in breast cancer cells was monitored by flow cytometry. The percentage of Annexin V-FITC positive cells to the total cells was shown in the bar graphs. *P<0.05 compared with control.
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pone-0065138-g006: Knockdown of MCL-1 suppresses cell proliferation, clonogenicity and induces cell apoptosis.A. Does effect and time effect of transfection of MCL-1-siRNA on the proliferation of MDA-MB-231 and MCF-7 cells. B. The functional role of MCL-1 in breast cancer cell growth was analyzed by colony formation of MDA-MB-231 and MCF-7 cells. The evaluation of colony numbers was shown in the panel. C. Influence of MCL-1 on apoptosis in breast cancer cells was monitored by flow cytometry. The percentage of Annexin V-FITC positive cells to the total cells was shown in the bar graphs. *P<0.05 compared with control.

Mentions: In order to address the functional role of MCL-1 in breast cancer cells, MDA-MB-231 and MCF-7 cells were transfected with MCL-1-specific siRNAs. The results of MTT assay indicated that knockdown of MCL-1 led to inhibition of cell growth and proliferation both in these two cell lines (Fig. 6A). A colony-forming assay was carried out to evaluate the effect of MCL-1 on the clonogenicity ability of breast cancer cells. As shown in Fig. 6B, MCL-1-siRNA-transfected cells displayed fewer and smaller colonies compared with control-siRNA transfectants (P<0.05). Furthermore, flow cytometry analysis revealed that transfection with MCL-1-siRNA significantly increased the number of apoptotic cells in both MDA-MB-231 (0.5% vs 8.4%; P<0.05) and MCF-7 (0.9% vs 7.4%; P<0.05) cells(Fig. 6C).


MiR-26a inhibits proliferation and migration of breast cancer through repression of MCL-1.

Gao J, Li L, Wu M, Liu M, Xie X, Guo J, Tang H, Xie X - PLoS ONE (2013)

Knockdown of MCL-1 suppresses cell proliferation, clonogenicity and induces cell apoptosis.A. Does effect and time effect of transfection of MCL-1-siRNA on the proliferation of MDA-MB-231 and MCF-7 cells. B. The functional role of MCL-1 in breast cancer cell growth was analyzed by colony formation of MDA-MB-231 and MCF-7 cells. The evaluation of colony numbers was shown in the panel. C. Influence of MCL-1 on apoptosis in breast cancer cells was monitored by flow cytometry. The percentage of Annexin V-FITC positive cells to the total cells was shown in the bar graphs. *P<0.05 compared with control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672200&req=5

pone-0065138-g006: Knockdown of MCL-1 suppresses cell proliferation, clonogenicity and induces cell apoptosis.A. Does effect and time effect of transfection of MCL-1-siRNA on the proliferation of MDA-MB-231 and MCF-7 cells. B. The functional role of MCL-1 in breast cancer cell growth was analyzed by colony formation of MDA-MB-231 and MCF-7 cells. The evaluation of colony numbers was shown in the panel. C. Influence of MCL-1 on apoptosis in breast cancer cells was monitored by flow cytometry. The percentage of Annexin V-FITC positive cells to the total cells was shown in the bar graphs. *P<0.05 compared with control.
Mentions: In order to address the functional role of MCL-1 in breast cancer cells, MDA-MB-231 and MCF-7 cells were transfected with MCL-1-specific siRNAs. The results of MTT assay indicated that knockdown of MCL-1 led to inhibition of cell growth and proliferation both in these two cell lines (Fig. 6A). A colony-forming assay was carried out to evaluate the effect of MCL-1 on the clonogenicity ability of breast cancer cells. As shown in Fig. 6B, MCL-1-siRNA-transfected cells displayed fewer and smaller colonies compared with control-siRNA transfectants (P<0.05). Furthermore, flow cytometry analysis revealed that transfection with MCL-1-siRNA significantly increased the number of apoptotic cells in both MDA-MB-231 (0.5% vs 8.4%; P<0.05) and MCF-7 (0.9% vs 7.4%; P<0.05) cells(Fig. 6C).

Bottom Line: MicroRNAs are a family of small non-coding RNAs 18-25 nucleotides in length that post-transcriptionally modulate gene expression.MCL-1, an anti-apoptotic member of the Bcl-2 family, as novel targets of miR-26a was found to be in reverse correlation with ectopic expression of miR-26a and knockdown of MCL-1 phenocopied the effect of miR-26a in breast cancer cell lines.Thus, miR-26a impacts on cell proliferation and migration of breast cancer by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of MCL-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.

ABSTRACT
Breast cancer is the most commonly malignancies in women. MicroRNAs are a family of small non-coding RNAs 18-25 nucleotides in length that post-transcriptionally modulate gene expression. MiR-26a has been reported as a tumor suppressor microRNA in breast cancer, which is attributed mainly to targeting of MTDH and EZH2, however, the expression profile and therapeutic potential of miR-26a is still unclear. Here we demonstrate that miR-26a is down-regulated in breast cancer cells and clinical specimens and its modulation in breast cancer cells regulates cell proliferation, colony formation, migration and apoptosis. MCL-1, an anti-apoptotic member of the Bcl-2 family, as novel targets of miR-26a was found to be in reverse correlation with ectopic expression of miR-26a and knockdown of MCL-1 phenocopied the effect of miR-26a in breast cancer cell lines. It was further explored that miR-26a increased sensitivity of breast cancer cells to paclitaxel in which MCL-1 was involved. Thus, miR-26a impacts on cell proliferation and migration of breast cancer by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of MCL-1.

Show MeSH
Related in: MedlinePlus