CircHIPK3 Promotes Gemcitabine (GEM) Resistance in Pancreatic Cancer Cells by Sponging miR-330-5p and Targets RASSF1

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Pancreatic cancer (PC) is a leading cause of cancer-related mortality worldwide.
• Gemcitabine (GEM) is a primary chemotherapy for PC, but chemoresistance limits its efficacy.
• Novel biomarkers for early diagnosis and treatment of GEM-resistant PC are urgently needed.

Purpose of the Study:

• To investigate the role of circular RNA homeodomain-interacting protein kinase 3 (circHIPK3) in pancreatic cancer.
• To determine the impact of circHIPK3 on gemcitabine resistance and its underlying molecular mechanisms.

Main Methods:

• Expression analysis of circHIPK3 in pancreatic cancer tissues and cells using RT-PCR.
• In vitro and in vivo experiments to assess the effects of circHIPK3 knockdown on cancer cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis.
• Bioinformatic analysis, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) to elucidate the interaction between circHIPK3, miR-330-5p, and RASSF1.

Main Results:

• circHIPK3 expression was significantly upregulated in pancreatic cancer tissues and cells, particularly in GEM-resistant cases.
• Knockdown of circHIPK3 inhibited proliferation, invasion, and migration, suppressed EMT, and enhanced apoptosis in vitro, and reduced tumor growth in vivo.
• circHIPK3 acts as a molecular sponge for miR-330-5p, which directly targets the 3' untranslated region (UTR) of RASSF1.

Conclusions:

• circHIPK3 promotes gemcitabine resistance in pancreatic cancer by regulating RASSF1 expression via the miR-330-5p pathway.
• circHIPK3 influences key cellular processes including proliferation, invasion, migration, EMT, and apoptosis.
• circHIPK3 represents a promising novel biomarker and therapeutic target for GEM-resistant pancreatic cancer.