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Curcumin suppresses pancreatic cancer progression and glycolysis by modulating the circ_0001535/miR-126-5p/HIPK2 axis

Luoluo Wang1, Xiang Wu1, Yi Ruan1

  • 1Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.

Journal of Drug Targeting
|April 8, 2026
PubMed

Insights

Curcumin inhibits pancreatic cancer (PC) by upregulating circ_0001535, a circular RNA that suppresses tumor growth. This mechanism involves the circ_0001535/miR-126-5p/HIPK2 pathway, enhancing curcumin

Area of Science:

  • Molecular Oncology
  • Non-coding RNA Biology
  • Cancer Therapeutics

Background:

  • Curcumin demonstrates anticancer properties in pancreatic cancer (PC) via multiple molecular pathways.
  • The precise regulatory roles of non-coding RNA networks in curcumin's effects on PC remain unclear.
  • Understanding circRNA-driven networks is crucial for elucidating curcumin's therapeutic mechanisms in PC.

Purpose of the Study:

  • To investigate the functional role of circRNAs in pancreatic cancer progression.
  • To elucidate the specific circRNA-driven regulatory networks influenced by curcumin.
  • To determine the therapeutic potential of targeting circ_0001535 in combination with curcumin.

Main Methods:

  • Assessed cellular functions (viability, clonogenicity, migration, invasion) using CCK-8, colony formation, and Transwell assays.
  • Measured glycolytic activity with commercial kits and Seahorse XP 96.
  • Detected RNA and protein expression via RT-qPCR and Western blot; verified circRNA-miRNA interactions using dual-luciferase reporter assays and RIP; evaluated in vivo tumor suppression in mouse xenograft models.

Main Results:

  • Observed downregulation of circ_0001535 and HIPK2, with elevated miR-126-5p expression in PC tissues.
  • Curcumin treatment significantly upregulated circ_0001535, suppressed malignant cellular behaviors, and inhibited tumor growth in vivo.
  • Mechanistically, circ_0001535 acts as a sponge for miR-126-5p, thereby modulating HIPK2 expression. Overexpression of circ_0001535 potentiated curcumin's antitumor effects.

Conclusions:

  • Curcumin inhibits pancreatic cancer progression primarily by upregulating circ_0001535.
  • The circ_0001535/miR-126-5p/HIPK2 signaling axis is a key mechanism mediating curcumin's effects.
  • This study offers novel insights into curcumin's therapeutic potential in PC, highlighting circ_0001535 as a potential therapeutic target.
Keywords:
Curcumincirc_0001535glycolysismechanistic studypancreatic cancer

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