tRF-Gly-CCC-012 enhances malignant process in pancreatic cancer via the HNRNPC/PHGDH axis

Area of Science:

• Molecular Biology
• Oncology
• Biochemistry

Background:

• Pancreatic cancer (PC) presents a significant clinical challenge due to late diagnosis and aggressive behavior.
• tRNA-derived fragments (tRFs) are emerging as critical regulators in various cancers, including PC.
• Identifying novel molecular players is crucial for developing effective PC diagnostics and therapeutics.

Purpose of the Study:

• To investigate the role of tRF-Gly-CCC-012 in pancreatic cancer.
• To elucidate the molecular mechanisms underlying tRF-Gly-CCC-012's function in PC.
• To evaluate tRF-Gly-CCC-012 as a potential biomarker and therapeutic target for PC.

Main Methods:

• Fluorescence in situ hybridization (FISH) and RNA isolation to determine tRF-Gly-CCC-012 localization.
• In vitro knockdown and overexpression studies in PC cell lines and organoids.
• In vivo xenograft models to assess the effect of tRF inhibition on tumor growth.
• RNA sequencing, RNA pulldown assays, and mass spectrometry to identify molecular interactions and pathways.

Main Results:

• tRF-Gly-CCC-012 was highly expressed in PC tissues and predominantly localized in the cytoplasm.
• Knockdown of tRF-Gly-CCC-012 suppressed PC cell aggressiveness and tumor growth in vivo.
• Overexpression of tRF-Gly-CCC-012 promoted PC malignancy.
• tRF-Gly-CCC-012 upregulates PHGDH by binding to HNRNPC, inhibiting its degradation and promoting serine synthesis.
• tRF-Gly-CCC-012 enhances HNRNPC protein stability, leading to PHGDH upregulation and PC progression.

Conclusions:

• tRF-Gly-CCC-012 is a key driver of pancreatic cancer progression.
• The tRF-Gly-CCC-012/HNRNPC/PHGDH axis represents a novel mechanism in PC pathogenesis.
• tRF-Gly-CCC-012 shows promise as a diagnostic biomarker and therapeutic target for pancreatic cancer.