SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner

Jiajin Wu1, Chenkui Miao1, Yuhao Wang1

  • 1Department of Urology, The First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital, No. 300 Guangzhou Road, Nanjing, 210029, China.

Abstract

Insights

SPTBN1 is down-regulated in kidney cancer (ccRCC). Its loss promotes tumor growth by activating glycolysis, suggesting SPTBN1 as a potential therapeutic target for ccRCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Renal clear cell carcinoma (ccRCC) is the most common kidney cancer.
  • Identifying prognostic biomarkers is crucial for ccRCC management.
  • The role of SPTBN1 in ccRCC pathogenesis was previously unknown.

Purpose of the Study:

  • To investigate the biological function and molecular mechanism of SPTBN1 in ccRCC.
  • To determine the potential of SPTBN1 as a biomarker or therapeutic target for ccRCC.

Main Methods:

  • Utilized single-cell and bulk RNA sequencing, tissue microarrays, qPCR, and Western blotting to assess SPTBN1 expression.
  • Generated and analyzed ccRCC cell line models with SPTBN1 gain or loss of function.
  • Conducted in vitro and in vivo assays, along with molecular experiments (Actinomycin D, RIP, inhibitor studies, rescue experiments) to elucidate mechanisms.

Main Results:

  • SPTBN1 expression was found to be significantly downregulated in ccRCC tissues.
  • Knockdown of SPTBN1 promoted ccRCC cell proliferation and tumor growth in vitro and in vivo.
  • Overexpression of SPTBN1 inhibited ccRCC progression.
  • SPTBN1 regulates ccRCC progression through the GPT2-dependent glycolysis pathway.
  • SPTBN1, as an RNA-binding protein, controls GPT2 mRNA stability, with GPT2 expression inversely correlated to SPTBN1.

Conclusions:

  • SPTBN1 is significantly downregulated in ccRCC and acts as a tumor suppressor.
  • SPTBN1 knockdown promotes ccRCC progression by activating GPT2-dependent glycolysis.
  • SPTBN1 represents a potential therapeutic target for ccRCC treatment.

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