Long noncoding RNA H19 acts as a miR‐340‐3p sponge to promote epithelial‐mesenchymal transition by regulating YWHAZ expression in paclitaxel‐resistant breast cancer cells

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Abstract
Breast cancer (BC) is the leading cause of cancer‐related death in women worldwide and one of the most prevalent malignancy. In recent years, increasing evidence had illuminated that long noncoding RNAs (lncRNAs) serve as critical factors in multiple tumor progression, including BC. Emerging references had indicated that the lncRNA H19 acts as significant roles in tumor progression and epithelial‐mesenchymal transition (EMT). However, the underlying molecular mechanisms and biological roles of H19 in BC invasion, metastasis and EMT are still unclear. In this study, it was detected that the expression level of H19 was increased in BC paclitaxel‐resistant (PR) cells subline (MCF‐7/PR) in comparison with MCF‐7 parental cells. In vitro, there were demonstrated that H19 overexpression promoted BC cells proliferation, metastasis, invasion and EMT procedures, and suppressed cells apoptosis. Whereas, H19 suppression resulted in the contrary biological effects. Besides, bioinformatics tools and dual‐luciferase reporters assays indicated that miR‐340‐3p could act as a potential target gene of H19, the underlying mechanism studies proved that H19 could act as a competing endogenous RNA (ceRNA) via competitively binding miR‐340‐3p to promote BC cell proliferation, metastasis and EMT by regulating tyrosine 3‐monooxygenase/tryptophan 5‐monooxygenase activation protein zeta (YWHAZ) and potentiate the Wnt/β‐catenin signaling in BC cells. In summary, our findings demonstrated that H19 could act as a ceRNA in BC progression, metastasis and EMT through modulating miR‐340‐3p/YWHAZ axis and activating the canonical Wnt/β‐catenin signaling pathway, indicating that H19 might act as an underlying therapeutic target and prognostic biomarker for BC therapy.
Funding Information
  • Key Program of Anhui Educational Committee (KJ2019A0297)
  • Key Program of College Discipline (Major) Top-Notch Talent Academic Subsidize of Anhui (gxbjZD27, 2017H110)
  • Key Projects of Anhui Province University Outstanding Youth Talent Support Program (gxyqZD2019037)
  • Major Program of Anhui Educational Committee (KJ2019ZD28)
  • Scientific Research Foundation of Bengbu Medical College (BYKY1810ZD)
  • tes Research of Bengbu Medical College (Byycx1808)

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