LINC-PINT suppresses the progression of acute myeloid leukemia via miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway.

BACKGROUND

Long noncoding RNA (lncRNA) long intergenic non-protein-coding RNA, p53-induced transcript (LINC-PINT) has shown a crucial role in cancer cells. However, its function in acute myeloid leukemia (AML) is unclear.

METHODS

The expression levels of LINC-PINT and miR-767-5p in AML patients were measured through quantitative real-time PCR. The interaction between miR-767-5p and LINC-PINT or suppressor of zeste 12 (SUZ12) was verified by RNA immunoprecipitation (RIP) assay and luciferase reporter assay. SUZ12-mediated JAK/STAT signaling pathway was further confirmed using western blotting and immunoprecipitation. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by CCK-8 and flow cytometry. Tumor formation was examined by a nude mice model in vivo.

RESULTS

The low expression of LINC-PINT was significantly related to ELN risk stratification (p = 0.028). Ectopic expression of LINC-PINT restrained the proliferation and cell cycle G1/S transition and promoted apoptosis in AML cell lines (THP-1 and HL-60). LINC-PINT overexpression curbed tumor growth. LINC-PINT positively regulated SUZ12 by functioning as a sponge of miR-767-5p. There was a negative correlation between miR-767-5p and LINC-PINT in AML (r = -0.3316, p = 0.0336). Co-expression of miR-767-5p reversed the impacts of LINC-PINT on AML cells. MiR-767-5p enhanced the aggressiveness of AML, which was counteracted by overexpression of SUZ12. Additionally, SUZ12 downregulated HDAC1 to reduce STAT3 phosphorylation and acetylation in AML cells.

CONCLUSIONS

Overall, LINC-PINT serves as a tumor suppressor in AML through the miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway, presenting a potential therapeutic target for AML.