Abstract
Breast cancer is still the most common and leading cause of cancer-related deaths in women worldwide. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have shown key regulator roles in various cancers. Previous reports have identified miR-125b as a critical tumor suppressor in breast cancer. However, the role of lncRNAs in breast cancer is far from well-characterized. In this study, we identified a novel lncRNA LINC01787, which specifically binds pre-miR-125b, inhibits the binding between DICER and pre-miR-125b, represses the processing of pre-miR-125b by DICER, and therefore induces pre-miR-125b accumulation and represses mature miR-125b generation. Functional assays showed that LINC01787 promotes breast cancer cell proliferation and migration and breast cancer xenograft growth in vivo, which is abolished by the mutation of pre-miR-125b binding sites on LINC01787 or overexpression of miR-125b. Furthermore, LINC01787 is up-regulated in breast cancer tissues and is associated with advanced stages and poor survival. The expression of LINC01787 is inversely associated with that of miR-125b in breast cancer tissues. In conclusion, our findings identified a novel up-regulated and oncogenic lncRNA LINC01787 in breast cancer, which binds pre-miR-125b and represses mature miR-125b generation. Our data suggests LINC01787 as a potential prognostic biomarker and therapeutic target for breast cancer.
Highlights
According to global cancer statistics in 2018, breast cancer remains the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide [1]
The nearly completely consistent sequences between LINC01787 and stem regions of both pre-miR-125b implied that LINC01787 may bind another stranded of stem regions of both pre-miR-125b (Figures 1A,B). Both pre-miR-125b and LINC01787 were mainly located in the cytoplasm in breast cancer cells (Figures S1A,B), which support the potential interaction between LINC01787 and pre-miR-125b
The previously reported binding between pre-miR483 and DICER was used to verify RNA Immunoprecipitation (RIP) efficiencies, which was not regulated by LINC01787 (Figures S1F,G)
Summary
According to global cancer statistics in 2018, breast cancer remains the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide [1]. Chemotherapy, radiotherapy, endocrine therapy, molecular-targeted therapy, and immunotherapy, breast cancer remains the cause of a vast number of deaths [2,3,4,5]. LINC01787 Drives Breast Cancer Progression that most of human transcriptomes are non-coding RNAs [10]. Among these great number of non-coding RNAs, microRNA (miRNA) and long non-coding RNA (lncRNA) are two classes of regulatory RNAs, that play important roles in various physiological and pathological processes [11,12,13,14]. The tumor suppressive roles of miR-125b in breast cancer were verified in other reports with several new miR-125b targets being identified, including ETS and SNAI1 [24, 25]
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