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. 2025 Aug 20.
doi: 10.1007/s00210-025-04522-z. Online ahead of print.

HRASLS2 promotes the growth and glycolysis of pancreatic cancer by enhancing the stability of ASPH

Ying Ling  1 , Chunhui Xi  1 , Jun Wang  1 , Luting Wang  1 , Xin Cao  1 , Juan Liu  2
Affiliations

HRASLS2 promotes the growth and glycolysis of pancreatic cancer by enhancing the stability of ASPH

Ying Ling et al. Naunyn Schmiedebergs Arch Pharmacol. .

Abstract

Pancreatic cancer remains one of the deadliest forms, with limited treatment options and a grim prognosis. However, the role of HRASLS2 in pancreatic adenocarcinoma (PAAD) is still not fully understood. This study aimed to investigate the role of HRAS-like suppressor family 2 (HRASLS2) and its potential mechanisms in PAAD. In this study, HRASLS2 expression and its prognostic significance were analyzed using online databases. Cell Counting Kit-8 and Ethynyl-20-deoxyuridine (EdU) assays were used to assess the growth activity of pancreatic cancer cells. Glucose consumption, lactic acid production, and extracellular acidification rate (ECAR) were measured to assess glycolytic activity. A xenograft model was employed to explore the role of HRASLS2 in vivo. Here, we found that the expression of HRASLS2 was higher in PAAD tissues, positively associated with copy number variations, and negatively correlated with promoter methylation. High levels of HRASLS2 were linked to poor prognosis and tumor immune microenvironment. Functionally, HRASLS2 promoted the growth of pancreatic cancer cells both in vivo and in vitro. HRASLS2 knockdown inhibited the growth and glycolysis of pancreatic cancer cells. Mechanistically, HRASLS2 interacted with aspartate β-hydroxylase (ASPH) protein and increased its stability. Overexpression of ASPH reversed the inhibitory effects on cell growth and glycolysis caused by knockdown of HRASLS2 in pancreatic cancer cells. This investigation revealed a novel mechanism of HRASLS2 in promoting the growth and glycolysis of PAAD by upregulating ASPH protein and indicated that HRASLS2 may be a potential therapeutic strategy for PAAD.

Keywords: ASPH; Glycolysis; HRASLS2; Pancreatic cancer; Prognosis.

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Conflict of interest statement

Declarations. Ethical approval: All experimental procedures were approved by the Ethics Committee of Affiliated Hospital of North Sichuan Medical College (approval number: 2025029). Competing interests: The authors declare no competing interests.

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