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CircLPAR3 knockdown suppresses esophageal squamous cell carcinoma cell oncogenic phenotypes and Warburg effect

Yao Cheng1, Zhenchuan Ma1, Shiyuan Liu1

  • 1Department of Thoracic Surgery, 12480Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Human & Experimental Toxicology
|December 9, 2022
PubMed
Abstract

Insights

Circular RNA lysophosphatidic acid receptor 3 (circLPAR3) promotes esophageal squamous cell carcinoma (ESCC) by enhancing the Warburg effect. Knockdown of circLPAR3 inhibits ESCC progression via the miR-873-5p/LDHA pathway, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Circular RNAs (circRNAs) are implicated in various cancers.
  • Esophageal squamous cell carcinoma (ESCC) is a significant malignancy.
  • The role of circRNA lysophosphatidic acid receptor 3 (circLPAR3) in ESCC and its associated Warburg effect requires elucidation.

Purpose of the Study:

  • To investigate the clinical significance and biological functions of circLPAR3 in ESCC.
  • To explore the regulatory mechanisms of circLPAR3 in ESCC cell phenotypes and the Warburg effect.
  • To determine if circLPAR3 acts as a therapeutic target for ESCC.

Main Methods:

  • Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot for gene and protein expression.
  • Assessment of Warburg effect via glucose uptake and lactate production assays.
  • In vitro assays (MTT, EdU, flow cytometry, wound healing, Transwell) for cell proliferation, apoptosis, and metastasis.
  • Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays to confirm molecular interactions.
  • In vivo studies using xenograft mouse models.

Main Results:

  • CircLPAR3 expression was elevated in ESCC tissues and cells.
  • CircLPAR3 knockdown suppressed ESCC cell proliferation, metastasis, and the Warburg effect, while inducing apoptosis in vitro.
  • CircLPAR3 knockdown impeded tumor growth and the Warburg effect in vivo.
  • CircLPAR3 acts as a molecular sponge for miR-873-5p, regulating lactate dehydrogenase A (LDHA) expression.
  • The miR-873-5p/LDHA axis mediated the effects of circLPAR3 on ESCC progression.

Conclusions:

  • CircLPAR3 knockdown inhibits ESCC growth, metastasis, and the Warburg effect through the miR-873-5p/LDHA pathway.
  • CircLPAR3 represents a promising molecular target for ESCC therapy.
Keywords:
CircLPAR3esophageal squamous cell carcinomalactate dehydrogenase AmiR-873-5ptumorigenesiswarburg effect

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