Abstract
Breast cancer stem cells (BCSCs) have high tumorigenicity and invasiveness, which contributes to recurrence and metastasis. The long non-coding RNA SOX21-AS1 has been previously reported to modulate the properties of breast cancer stem cells via targeting SOX2, although the underlying molecular mechanisms remain unclear. To investigate this issue, we first confirmed that the expression level of SOX21-AS1 is increased in breast cancer tissues and cell lines (MCF-7, MDA-MB-231, CSC-MCF-7, CSC-MDA-MB-231), especially in BCSCs. We demonstrated that SOX21-AS1 promotes the stemness of CSC-MCF-7 cells through western blot detection of stemness-related proteins, as well as side population and sphere formation assays. Overexpression of SOX21-AS1 enhanced the proliferation, migration and invasion of CSC-MCF-7 cells. We also observed that SOX21-AS1 inhibited the Hippo pathway. SOX21-AS1 enhanced the stemness, migration and invasion of CSC-MCF-7 cells by increasing the nuclear localization of YAP and decreasing the level of pYAP. Overall, we conclude that SOX21-AS1 may promote the stemness viability, proliferation, migration and invasion of BCSCs by inhibiting the Hippo pathway. Our findings provide insights into potential biomarkers and prognostic measures for the treatment of breast cancer.
Highlights
Breast cancer is a type of malignancy and the global leading cause of cancer-related death in women [1]
SOX21-AS1 is highly expressed in breast cancer tissues and cell lines
The discovery of tumor stem cells has confirmed that they play important roles in tumor survival, proliferation, metastasis and relapse [21]
Summary
Breast cancer is a type of malignancy and the global leading cause of cancer-related death in women [1]. Studies have confirmed that stem cell-like cell populations exist in tumor tissues [2,3,4]. Breast cancer stem cells (BCSCs) with self-renewal ability and multidirectional differentiation potential in breast cancer tissues are closely associated with the occurrence, development, post-treatment metastasis and the relapse of breast cancer [5,6]. Increasing evidence shows that lncRNA plays an important role in cell differentiation, proliferation and apoptosis [8]. The role of lncRNA dysregulation in tumorigenesis and development has attracted more and more attention. Recent studies have shown that lncRNA SOX21-AS1 is located at chromosome 13q32.1 and transcribed into a 2986 nucleotide transcript, which exerts important functions in tumorigenesis and maintenance of tumor stem cell characteristics [9].
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