Jinrong Xie, Jianchun Gu, Wenjie Lv, Limin Cheng, Shuxian Chen, Ran Wu, Yan Liang, Meiling Zhu, Siyu Chen, Mawei Jiang, Jun Su
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Long Noncoding RNA MNX1-AS1 Promotes Tumorigenesis of Breast Cancer by Binding IGF2BP1 to Activate c-MET.
Breast cancer is the most common malignancy that threaten women's health seriously. Many studies have shown that long noncoding RNAs can play significant role in the tumorigenesis of breast cancer. By analyzing the TCGA breast cancer genome data and transcriptome data, we found that copy number amplification drives the activation of long noncoding RNA MNX1-AS in breast cancer and indicates poor prognosis. Functionally, MNX1-AS1 could regulate pathogenesis of breast cancer in vitro and in vivo. Mechanistically, MNX1-AS1 could bind IGF2BP1, which increased the interaction of IGF2BP1 with MET mRNA to promote its stability, thus promoting tumorigenesis of breast cancer. Moreover, combination of MNX1-AS1 inhibition and MET small molecule inhibitor (PHA-665752, PHA) exhibited better antitumor efficacy in xenograft model, suggesting the therapeutic potential. Overall, our findings indicated that MNX1-AS1/MET regulatory axis may serve as a potential therapeutic target in breast cancer.
期刊介绍：
Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.
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