title: Upregulated microRNA-301a in breast cancer promotes tumor metastasis by targeting PTEN and activating Wnt/β-catenin signaling.
abstract: MicroRNAs (miRNAs) are strongly implicated in many cancers, including breast cancer. Recently, microRNA-301a (miR-301a) has been proved to play a substantial role in gastric cancer, but its functions in the context of breast cancer remain unknown. Here we report that miR-301a was markedly upregulated in primary tumor samples from patients with distant metastases and pro-metastatic breast cancer cell lines. Gain-of-function and loss-of-function studies showed that ectopic overexpression of miR-301a promoted breast cancer cell migration, invasion and metastasis both in vitro and in vivo. Notably, Wnt/β-catenin signaling was hyperactivated in metastatic breast cancer cells that express miR-301a, and mediated miR-301a-induced invasion and metastasis. Furthermore, miR-301a directly targeted and suppressed PTEN, one negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that miR-301a maintains constitutively activated Wnt/β-catenin signaling by directly targeting PTEN, which promotes breast cancer invasion and metastasis. Taken together, our findings reveal a new regulatory mechanism of miR-301a and suggest that miR-301a might be a potential target in breast cancer therapy.
authors: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Fei
authors: F
authors: Ma
authors: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Jianguo
authors: J
authors: Zhang
authors: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Lei
authors: L
authors: Zhong
authors: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Lei
authors: L
authors: Wang
authors: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Yansong
authors: Y
authors: Liu
authors: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Yimin
authors: Y
authors: Wang
authors: Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Lin
authors: L
authors: Peng
authors: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: baoliangguo2013@163.com.
authors: Baoliang
authors: B
authors: Guo
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C550735:MIRN301A microRNA, human; D035683:MicroRNAs; D051153:Wnt Proteins; D051176:beta Catenin; D051059:PTEN Phosphohydrolase
keywords: Breast cancer; LEF; ORF; PTEN; T cell factor; TCF; UTR; Wnt/β-catenin; lymphoid enhancer factor; mir-301a; open reading frame; phosphatase and tensin homolog; untranslated region