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Knockdown of HSDL2 inhibits lung adenocarcinoma progression via down-regulating AKT2 expression

Yujia Shi1,2, Zhengdao Mao2, Yanhua Huang2

  • 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.

Bioscience Reports
|March 27, 2020
PubMed

Insights

Hydroxysteroid dehydrogenase-like 2 (HSDL2) promotes lung adenocarcinoma growth and metastasis by upregulating AKT2. Knocking down HSDL2 inhibits cancer progression and improves patient survival, revealing HSDL2 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Expression Analysis

Background:

  • Lung adenocarcinoma is a major cause of cancer mortality.
  • The molecular mechanisms driving lung adenocarcinoma progression require further elucidation.
  • The role of hydroxysteroid dehydrogenase-like 2 (HSDL2) in lung cancer is not well understood.

Purpose of the Study:

  • To investigate the role of HSDL2 in lung adenocarcinoma.
  • To identify the molecular mechanisms by which HSDL2 influences lung cancer progression.
  • To assess the therapeutic potential of targeting HSDL2.

Main Methods:

  • Gene knockdown using small interfering RNA (siHSDL2) to reduce HSDL2 expression.
  • In vitro assays (proliferation, cell cycle, apoptosis, clone-formation, invasion, migration) and in vivo studies (growth, metastasis).
  • Microarray hybridization and gene expression analysis to profile mRNA changes; Western blotting for protein analysis; rescue experiments with AKT2 overexpression.

Main Results:

  • HSDL2 was significantly upregulated in lung adenocarcinoma tissues, correlating with worse patient survival.
  • HSDL2 knockdown inhibited lung adenocarcinoma cell proliferation, migration, invasion, and metastasis both in vitro and in vivo.
  • HSDL2 knockdown altered gene expression, notably downregulating AKT2 and BIRC3, and upregulating ERK phosphorylation; AKT2 overexpression rescued the inhibitory effects of HSDL2 knockdown.

Conclusions:

  • HSDL2 acts as an oncogene promoting lung adenocarcinoma growth and metastasis.
  • HSDL2 facilitates lung cancer progression primarily through the AKT2 signaling pathway.
  • HSDL2 represents a promising therapeutic target for lung adenocarcinoma treatment.
Keywords:
gene chiphydroxysteroid dehydrogenase-like 2lung adenocarcinomanon-small cell lung cancerprognosis

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