microRNA-22 downregulation of galectin-9 influences lymphocyte apoptosis and tumor cell proliferation in liver cancer

Abstract

Abstract. plays an important role in both the immune response and tumor progression, while microRNAs act as tumor regulators to mediate tumorigenesis. However, the underlying molecular mechanisms remain unknown. In the present study, we investigated the relationship between Gal-9 and microRNA-mediated regulation in liver cancer. We examined Gal-9 expression using qRT-PCR and western blot analysis and found that it was markedly upregulated in human liver cancer cells compared with the level in normal hepatocytes. We co-cultured peripheral blood mononuclear cells (PBMCs) and tumor cells and observed that Gal-9 induced lymphocyte apoptosis and tumor cell immune escape using flow cytometric analysis and WST-1 assay. We found that miR-22 was downregulated in liver cancer tissues and cell lines and confirmed that miR-22 directly targeted the Gal-9 3'UTR and negatively regulated Gal-9 expression by luciferase reporter assay and transfection of microRNA mimics. We also observed that the Gal-9/miR-22 axis may influence lymphocyte apoptosis and tumor cell proliferation. These studies contribute to a further understanding of the microRNA-mediated regulation of the Gal-9 pathway and elucidate novel therapeutic targets for liver cancer.

Molecular mechanisms and clinical applications of miR-22 in regulating malignant progression in human cancer (Review)

“…Additionally to the above, miR-22 has been reported to tightly repress cellular immune escape and proliferation and trigger apoptosis by targeting a variety of downstream molecules, such as Galectin-9, NET1 (neuro-epithelial transforming gene 1) and PAPST1, in liver cancer, chronic myeloid leukemia (CML) and medulloblastoma, respectively (21–23). In addition, not only could curcumin-induced miR-22 post-transcriptionally degrade oncogene Erbb3 in retinoblastoma, but also ectopic elevated miR-22 expression could directly target Erbb3 or EVI-1, subsequently causing the repression of PI3K/Akt cascade, the end result is inhibition of cellular proliferation, migration, invasion and metastasis in lung cancer and breast cancer, respectively (24–26).…”

miR-455-5p functions as a potential oncogene by targeting galectin-9 in colon cancer

“…The target prediction programs miRanda and TargetScan were used to predict and identify miRNAs that may target galectin-9. The present study identified four miRNAs (miR-22, 296-3p, 455-5p and 491-5p) that were potential regulators of galectin-9 (26).…”

“…Human GAPDH and U6 were used as the housekeeping genes for the amplifications. The PCR primers used in the present study were described previously (26).…”

“…The plasmid (p) cytomegalovirus (CMV) -galectin-9-3'-UTR wild-type (WT), pCMV-galectin-9-3'-UTR mutant (MU) and galectin-9 overexpression vector (Galectin-9/pcDNA3.1) were constructed as described previously (26). The specific primers for galectin-9 3'UTR-WT were: Forward, 5'-ATA GAA TTC GCG GCT TCC TGG CCC TG-3' and reverse, 5'-CGC AAG CTT TGA ATG TGC CAA CAA GCA-3'.…”

Microdomain forming proteins in oncogenesis

“…Наиболее изученные miR-21 (онкоген) и группа let-7 (микроРНК-онкосупрессоры), изменение экспрессии которых тес-но связано с различными этапами опухолевой прогрес-сии, также регулируют МОБ [84,100,102]. Существуют данные о регуляции флотиллина-1 miR-485 и miR-506 [103,104], флотиллина-2 miR-34а [105] и галектина-3 miR-22 [106]. Вышеупомянутые микроРНК часто об-наруживаются в составе экзосом.…”