Abstract
Mir-29 microRNA families are involved in regulation of various types of cancers. Although Mir-29 was shown to play an inhibitory role in tumorigenesis, the role of Mir-29 in breast cancer still remains obscure. In this study, we showed that Mir-29a is the dominant isoform in its family in mammary cells and expression of Mir-29a was down-regulated in different types of breast cancers. Furthermore, over-expression of Mir-29a resulted in significant slower growth of breast cancer cells and caused higher percentage of cells at G0/G1 phase. Consistent with this over-expression data, knockdown of Mir-29a in normal mammary cells lead to higher cell growth rate, and higher percentage of cells entering S phase. We further found that Mir-29a negatively regulated expression of B-Myb, which is a transcription factor associated with tumorigenesis. The protein levels of Cyclin A2 and D1 are consistent with the protein level of B-Myb. Taken together, our data suggests Mir-29a plays an important role in inhibiting growth of breast cancer cells and arresting cells at G0/G1 phase. Our data also suggests that Mir-29a may suppress tumor growth through down-regulating B-Myb.
Highlights
Breast cancer is the most common cancer diagnosed in women
Mir-29a is the dominant member of mir-29 family Mir-29 family is composed of three members Mir-29a, b and c, which are involved in tumorigenesis, chronic lymphocyte leukemia, acute myeloid leukemia and apoptosis [13,18]
Expression levels of Mir-29a are significantly lower in breast cancer cells when compared to those in normal mammary cells Previous studies have showed that Mir-29 isoforms are involved in suppression of tumorigenesis [3,15,19,20,21]
Summary
Breast cancer is the most common cancer diagnosed in women. there were noteworthy advances in the early diagnosis and treatment during the past several decades, breast cancer still stands as the leading cause of cancer death in women worldwide [1,2]. (after 2005), there is a growing interest in the roles of a new class of small non-coding RNAs, microRNAs (miRNAs) in breast cancer development [3,4]. MiR-29 family was reported to regulate specific genes associated with tissue invasion and metastasis in lung adenocarcinoma [8]. It has been reported that by inhibiting MMP2 activity, MiR-29 plays an important inhibitory role in APOBEC3G induced colon cancer migration and invasion [14]. Consistent with the data from studies on other types of cancer, MiR-29 family inhibits ovarian cancer development by targeting DNA methyltransferases 3A and 3B [15]
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