LINC01234 aggravates cell growth and migration of triple‐negative breast cancer by activating the Wnt pathway

• DOI: 10.1002/tox.23318
• Publication Date: 2021-06-26T12:12:27Z
• Authors: Feng Xiao; Hongyao Jia; Di Wu; Zhiru Zhang; Sijie Li; Jianjin Guo
• Keywords: 0303 health sciences; Triple Negative Breast Neoplasms; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Female; RNA, Long Noncoding; Wnt Signaling Pathway; Cell Proliferation

AbstractTriple‐negative breast cancer (TNBC) is a common cancer with increasing incidence and mortality in female. Increasing studies have revealed that long noncoding RNAs (lncRNAs) are novel molecules regulating tumors. Long intergenic non‐protein coding RNA 1234 (LINC01234) has been demonstrated to function as an oncogene in several tumors. However, the role of LINC01234 in TNBC remains unelucidated. Herein, RT‐qPCR showed that LINC01234 expression was upregulated in both TNBC tissues and cell lines. Functionally, knockdown of LINC01234 suppressed proliferation, migration, invasion, epithelial‐mesenchymal transition (EMT) process, and promoted apoptosis in TNBC cells. Xenograft mouse models revealed that LINC01234 downregulation inhibited TNBC tumor growth in vivo. Furthermore, LINC01234 was transcriptionally elevated by Sp1 transcription factor (SP1) in TNBC cells. Mechanistically, LINC01234 interacted with miR‐525‐5p and miR‐525‐5p targeted MEIS2. Rescue assays manifested that MEIS2 overexpression rescued the cellular processes inhibited by silenced LINC01234. Moreover, we validated that LINC01234 regulated the activation of the Wnt pathway through modulating MEIS2 in TNBC cells. In conclusion, LINC01234 aggravated TNBC cell growth, migration, invasion and EMT by modulating the miR‐525‐5p/MEIS2 axis and activating the Wnt/β‐catenin signaling pathway.