mTOR/miR-145-regulated exosomal GOLM1 promotes hepatocellular carcinoma through augmented GSK-3β/MMPs

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Golgi membrane protein 1 (GOLM1), also known as GP73, is a validated serum marker for hepatocellular carcinoma (HCC).
• Previous research established that the mammalian target of rapamycin (mTOR) pathway promotes HCC tumorigenesis by upregulating GOLM1 expression.

Purpose of the Study:

• To elucidate the regulatory relationship between mTOR, microRNA-145 (miR-145), and GOLM1 in HCC.
• To investigate the functional roles of GOLM1 and miR-145 in HCC progression and metastasis.
• To evaluate the potential of targeting the mTOR/miR-145/GOLM1 pathway for HCC treatment.

Main Methods:

• Investigated the effect of mTOR on miR-145 expression using molecular assays.
• Validated miR-145 targeting of GOLM1 at the coding sequence level.
• Analyzed the correlation between GOLM1 and miR-145 expression in human HCC tissues.
• Assessed the functional impact of GOLM1-enriched exosomes and miR-145 on HCC cell proliferation and migration.
• Examined the involvement of the glycogen synthase kinase-3β/matrix metalloproteinases (GSK-3β/MMPs) signaling axis.

Main Results:

• Demonstrated that mTOR acts as a negative regulator of miR-145 expression.
• Confirmed that miR-145 directly inhibits GOLM1 expression by targeting its coding sequence.
• Observed an inverse correlation between GOLM1 and miR-145 levels in human HCC tissues.
• Showed that GOLM1-enriched exosomes promote HCC cell proliferation and migration via the GSK-3β/MMPs pathway.
• Confirmed that miR-145 suppresses HCC tumorigenesis and metastasis.

Conclusions:

• The mTOR/miR-145/GOLM1 signaling pathway plays a critical role in HCC development and progression.
• miR-145 acts as a tumor suppressor by inhibiting GOLM1 and downstream signaling.
• Targeting the mTOR/miR-145/GOLM1 pathway represents a promising therapeutic strategy for hepatocellular carcinoma.