Circ_0084043-miR-134-5p axis regulates PCDH9 to suppress melanoma

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Melanoma exhibits low survival rates and resistance to therapies, necessitating novel therapeutic targets.
• Protocadherin 9 (PCDH9) is a potential tumor suppressor, but its role in melanoma requires further elucidation.
• Circular RNAs (circRNAs) are implicated in cancer progression, with their specific roles in melanoma pathogenesis under investigation.

Purpose of the Study:

• To investigate the regulatory role of the circ_0084043-miR-134-5p axis in melanoma.
• To determine the impact of Protocadherin 9 (PCDH9) on melanoma progression and its molecular mechanisms.
• To explore circ_0084043 as a potential therapeutic target for melanoma.

Main Methods:

• Quantitative real-time PCR and Western blotting were used to assess gene and protein expression levels.
• Lentivirus vectors were employed for ectopic expression and knockdown (KD) of PCDH9 and circ_0084043.
• Cell proliferation, invasion, and apoptosis assays were performed to evaluate melanoma cell behavior.
• In vivo studies using mouse models were conducted to assess tumor growth.

Main Results:

• PCDH9 overexpression inhibited melanoma cell proliferation and invasion while promoting apoptosis.
• circ_0084043 was overexpressed in melanoma and its KD suppressed malignant behaviors.
• circ_0084043 acted as a molecular sponge for miR-134-5p, indirectly regulating PCDH9.
• PCDH9 overexpression suppressed tumor growth in vivo, whereas PCDH9 KD promoted it.

Conclusions:

• PCDH9 functions as a tumor suppressor in melanoma, with its expression regulated by the circ_0084043-miR-134-5p axis.
• The circ_0084043-miR-134-5p-PCDH9 pathway influences key proteins involved in melanoma progression (Pyk2, RAC1, Cyclin D1, MMP2, MMP9).
• Targeting circ_0084043 presents a promising therapeutic strategy for melanoma, potentially impacting anti-PD-L1 effects.