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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

MCL-1 is the target of miR-26a.A. Putative miR-26a binding sites in the 3′UTR region of MCL-1 and interspecies conservation of seed matching sequences (gray box). B. Expression of MCL-1 in the 2 immortalized normal mammary epithelium cell lines and 4 breast cancer cell lines. C. Western blot assay for MCL-1 expression after MDA-MB-231 and MCF-7 cells were transfected with miR-26a for 48 hours. *P<0.05 compared with control.
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pone-0065138-g005: MCL-1 is the target of miR-26a.A. Putative miR-26a binding sites in the 3′UTR region of MCL-1 and interspecies conservation of seed matching sequences (gray box). B. Expression of MCL-1 in the 2 immortalized normal mammary epithelium cell lines and 4 breast cancer cell lines. C. Western blot assay for MCL-1 expression after MDA-MB-231 and MCF-7 cells were transfected with miR-26a for 48 hours. *P<0.05 compared with control.

Mentions: To figure out the mechanism by which miR-26a may perform in breast cancer, we made an online search of miR-26a targets by Targetscan. Among the hundreds of putative miRNA targets, we focused on MCL-1 as it is an anti-apoptotic member of the Bcl-2 family, which has been validated to be linked with tumorigenesis and resistance to chemotherapy by large amounts of evidences. Target scan showed that there was a miR-26a responsive sequence in 3′-UTR (3′untranslated region) of MCL-1, which was highly conserved among different species (Fig. 5A).


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)

MCL-1 is the target of miR-26a.A. Putative miR-26a binding sites in the 3′UTR region of MCL-1 and interspecies conservation of seed matching sequences (gray box). B. Expression of MCL-1 in the 2 immortalized normal mammary epithelium cell lines and 4 breast cancer cell lines. C. Western blot assay for MCL-1 expression after MDA-MB-231 and MCF-7 cells were transfected with miR-26a for 48 hours. *P<0.05 compared with control.
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Related In: Results  -  Collection

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

pone-0065138-g005: MCL-1 is the target of miR-26a.A. Putative miR-26a binding sites in the 3′UTR region of MCL-1 and interspecies conservation of seed matching sequences (gray box). B. Expression of MCL-1 in the 2 immortalized normal mammary epithelium cell lines and 4 breast cancer cell lines. C. Western blot assay for MCL-1 expression after MDA-MB-231 and MCF-7 cells were transfected with miR-26a for 48 hours. *P<0.05 compared with control.
Mentions: To figure out the mechanism by which miR-26a may perform in breast cancer, we made an online search of miR-26a targets by Targetscan. Among the hundreds of putative miRNA targets, we focused on MCL-1 as it is an anti-apoptotic member of the Bcl-2 family, which has been validated to be linked with tumorigenesis and resistance to chemotherapy by large amounts of evidences. Target scan showed that there was a miR-26a responsive sequence in 3′-UTR (3′untranslated region) of MCL-1, which was highly conserved among different species (Fig. 5A).

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