m6A reader IGF2BP2 promotes lymphatic metastasis by stabilizing DPP4 in papillary thyroid carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• Lymph node metastasis (LNM) is a primary driver of recurrence in papillary thyroid carcinoma (PTC).
• The precise molecular mechanisms underlying LNM in PTC are not fully understood.
• N6-methyladenosine (m6A) RNA modification is implicated in cancer progression and metastasis.

Purpose of the Study:

• To investigate the role of IGF2BP2 in PTC lymph node metastasis.
• To elucidate the underlying molecular mechanisms, including the involvement of m6A modification.
• To explore the therapeutic implications of targeting IGF2BP2 in PTC.

Main Methods:

• Human m6A epitranscriptomic microarray, m6A RNA immunoprecipitation (MeRIP), and RNA immunoprecipitation (RIP) assays.
• In vitro cell proliferation and invasion assays following IGF2BP2 knockdown.
• In vivo studies to assess the impact of IGF2BP2 on lymphatic metastasis.
• Analysis of IGF2BP2's effect on cisplatin sensitivity.

Main Results:

• IGF2BP2 expression was elevated in PTC and correlated positively with LNM.
• IGF2BP2 knockdown suppressed PTC cell proliferation, invasion, and in vivo lymphatic metastasis.
• IGF2BP2 activated the NF-κB pathway by enhancing DPP4 stability in an m6A-dependent manner.
• IGF2BP2 modulation affected PTC cell sensitivity to cisplatin therapy.

Conclusions:

• IGF2BP2 promotes papillary thyroid carcinoma lymphatic metastasis by stabilizing DPP4 through an m6A-dependent mechanism.
• IGF2BP2 represents a potential therapeutic target for inhibiting PTC metastasis.
• This study provides novel insights into the m6A-mediated regulation of lymphatic metastasis in PTC.