4.6 Article

WFDC21P promotes triple-negative breast cancer proliferation and migration through WFDC21P/miR-628/SMAD3 axis

Journal

FRONTIERS IN ONCOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.1032850

Keywords

WFDC21P; microRNA; N6-methyladenosine; epigenetics; triple-negative breast cancer

Categories

Funding

  1. National Natural Science Foundation of China
  2. Shandong Science and Technology Committee
  3. Education Department of Shandong Province
  4. Shandong Province Taishan Scholar Project
  5. [81772281]
  6. [31371321]
  7. [ZR2019MH022]
  8. [ZR2020KH015]
  9. [2019KJK014]
  10. [2021KJK005]
  11. [ts201712067]

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This study showed that the lncRNA-WFDC21P is significantly increased in triple-negative breast cancer (TNBC) and is associated with poor patient survival. Overexpression of WFDC21P promotes TNBC cell proliferation and metastasis. It interacts with miR-628-5p to negatively regulate Smad3-related gene expression, suppressing cell proliferation and metastasis. N6-methyladenosine (m6A) modification upregulates WFDC21P expression, and METTL3 plays a role in this process by promoting TNBC cell proliferation and metastasis.
Long non-coding RNAs (lncRNAs) modulate cell proliferation, cycle, and apoptosis. However, the role of lncRNA-WFDC21P in the tumorigenesis of triple-negative breast cancer (TNBC) remains unclear. Results of this study demonstrated that WFDC21P levels significantly increased in TNBC, which was associated with the poor survival of patients. WFDC21P overexpression significantly promoted TNBC cell proliferation and metastasis. WFDC21P interacted with miR-628-5p, which further suppressed cell proliferation and metastasis by negatively regulating Smad3-related gene expression. Recovery of miR-628-5p weakened the roles of WFDC21P in promoting the growth and metastasis of TNBC cells. Moreover,N6-methyladenosine (m6A) modification upregulated WFDC21P expression in the TNBC cells. WFDC21P and its m6A levels were increased after methyltransferase like 3 (METTL3) overexpression but reduced after METTL3 silencing. The proliferation and metastasis of TNBC cells were promoted by METTL3 overexpression but suppressed by METTL3 silencing. This study demonstrated the vital roles of WFDC21P and its m6A in regulating the proliferation and metastasis of TNBC cells via the WFDC21P/miR-628/SMAD3 axis.

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