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RELA/NEAT1/miR‐302a‐3p/RELA feedback loop modulates pancreatic ductal adenocarcinoma cell proliferation and migration
Author(s) -
Luo Zhen,
Yi ZhongJie,
Ou ZhengLin,
Han Tong,
Wan Tao,
Tang YongChang,
Wang ZhiChao,
Huang FeiZhou
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27039
Subject(s) - gene knockdown , cancer research , cell growth , downregulation and upregulation , oncogene , cell migration , biology , long non coding rna , microrna , cell , microbiology and biotechnology , cell cycle , apoptosis , gene , biochemistry , genetics
Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy due to distant metastasis. RELA, a major component of the NF‐κB pathway, could serve as an oncogene through activating proliferation or migration‐related gene expression, including NEAT1, a well‐known oncogenic long noncoding RNA. In the current study, the expression and function of RELA and NEAT1 in PDAC were examined. The potential upstream regulatory microRNAs of RELA were screened and verified for their correlation with RELA and NEAT1. The expression and function of the selected miR‐302a‐3p were evaluated. RELA and NEAT1 expression were upregulated in PDAC tissues, particularly in PDAC tissues with lymph node metastasis, and their expression correlated with clinical parameters. RELA overexpression promoted PDAC cell proliferation and migration, which could be partially attenuated by the NEAT1 knockdown. By binding to RELA, miR‐302a‐3p inhibited RELA expression, as well as PDAC cell proliferation and migration. RELA downstream NEAT1 expression was negatively regulated by miR‐302a‐3p; the suppressive effect of NEAT1 knockdown on PDAC cell proliferation and migration was partially attenuated by miR‐302a‐3p inhibition. Moreover, through direct binding, the expression of miR‐302a‐3p was also negatively regulated by NEAT1. The expression of miR‐302a‐3p was downregulated and negatively correlated with RELA or NEAT1 in tissue samples, indicating that rescuing miR‐302a‐3p expression may inhibit PDAC cell proliferation and migration through RELA/NEAT1. In summary, RELA, NEAT1, and miR‐302a‐3p form a feedback loop in PDAC to modulate PDAC cell proliferation and migration.