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SLCO4A1-AS1 promotes cell growth and induces resistance in lung adenocarcinoma by modulating miR-4701-5p/NFE2L1 axis

Yuxuan Wei1, Li Wei2, Jiwei Li2

  • 1Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou, China.

Cancer Medicine
|August 8, 2020
PubMed

Insights

Long noncoding RNA SLCO4A1-AS1 promotes lung adenocarcinoma (LUAD) growth and chemoresistance. It activates the WNT pathway by interacting with miR-4701-5p and targeting NFE2L1, driving LUAD progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • Long noncoding RNAs (lncRNAs) play crucial roles in human cancer development.
  • SLCO4A1 antisense RNA 1 (SLCO4A1-AS1) is implicated as an oncogenic regulator in other cancers, but its role in lung adenocarcinoma (LUAD) is unknown.

Purpose of the Study:

  • To investigate the function and mechanism of SLCO4A1-AS1 in lung adenocarcinoma (LUAD).
  • To explore the potential of SLCO4A1-AS1 as a therapeutic target in LUAD.

Main Methods:

  • Quantitative real-time PCR to assess SLCO4A1-AS1 expression levels in LUAD tissues and cells.
  • In vitro functional assays (proliferation, migration, cisplatin resistance) to evaluate the impact of SLCO4A1-AS1.
  • Mechanism studies including RNA immunoprecipitation, luciferase reporter assays, and Western blotting to elucidate the interaction between SLCO4A1-AS1, miR-4701-5p, and NFE2L1.
  • Rescue experiments to confirm the role of NFE2L1 in SLCO4A1-AS1-mediated effects.

Main Results:

  • SLCO4A1-AS1 was significantly upregulated in LUAD tissues and cells.
  • SLCO4A1-AS1 overexpression promoted LUAD cell proliferation, migration, and cisplatin resistance.
  • SLCO4A1-AS1 interacted with miR-4701-5p, which directly targeted NFE2L1.
  • NFE2L1 expression was positively correlated with SLCO4A1-AS1 and involved in SLCO4A1-AS1-induced LUAD cell growth via WNT pathway activation.

Conclusions:

  • SLCO4A1-AS1 acts as an oncogene in LUAD by promoting cell growth and chemoresistance.
  • The SLCO4A1-AS1/miR-4701-5p/NFE2L1 axis, involving WNT pathway activation, is a key mechanism driving LUAD progression.
  • SLCO4A1-AS1 represents a potential therapeutic target for lung adenocarcinoma.
Keywords:
NFE2L1SLCO4A1-AS1chemosensitivitylung adenocarcinomamiR-4701-5p

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