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Long non-coding RNA linc00921 suppresses tumorigenesis and epithelial-to-mesenchymal transition of triple-negative breast cancer via targeting miR-9-5p/LZTS2 axis

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机构: [1]Department of Plastic Surgery, Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China [2]Breast Disease Diagnostic and Therapeutic Center, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050035, Hebei, China [3]Department of Minimally Invasive Surgery, Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China [4]Department of Anus and Intestine Surgery, Second Affiliated Hospital of Hebei Medical University, ShijiazhuangHebei 050000, China
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关键词: Triple-negative breast cancer linc00921 LZTS2 miR-9-5p EMT

摘要:
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Dysregulation of long non-coding RNAs (lncRNAs) plays crucial roles in the initiation and progression of TNBC. In this study, we analyzed public GEO profiles to verify the key lncRNAs in TNBC. Linc00921 was selected for further study. Low expression of linc00921 was observed in 49 of 95 TNBC tissues. Low expression of linc00921 was correlated with poor postoperative disease-free survival (DFS) and overall survival (OS) of TNBC patients. Overexpression of linc00921 with lentivirus suppressed the proliferation, migration and invasion of TNBC cells. A luciferase reporter assay showed that linc00921 could sponge miR-9-5p in TNBC. Moreover, linc00921 and miR-9-5p occupied the same Argonaute-2 (Ago2) protein in TNBC cells. Leucine zipper tumor suppressor 2 (LZTS2) was recognized as a target gene of miR-9-5p, and thereby a linc00921/miR-9-5p/LZTS2 axis was identified in TNBC cells. Overexpression of linc00921 promoted nuclear export of beta-catenin, neutralized its function, and subsequently promoted epithelial-to-mesenchymal transition (EMT) in TNBC. A xenograft tumor mouse model showed that the miR-9-5p inhibitor upregulates LZTS2 expression and induce nuclear export of beta-catenin in TNBC. Thus, linc00921 upregulates LZTS2 by sponging miR-9-5p to suppress tumorigenesis and EMT of TNBC. Linc00921/miR-9-5p/LZTS2 axis may be a novel biomarker and therapeutic target for TNBC patients.

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出版当年[2022]版:
大类 | 3 区 生物学
小类 | 4 区 细胞生物学
最新[2025]版:
大类 | 3 区 生物学
小类 | 4 区 细胞生物学
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出版当年[2022]版:
Q2 CELL BIOLOGY
最新[2023]版:
Q3 CELL BIOLOGY

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第一作者机构: [1]Department of Plastic Surgery, Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
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