Anti-RUNX3 (aa 194-279) polyclonal antibody

Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3) are transcription factors that promote multiple myeloma (MM) proliferation. The immunomodulatory imide drug (IMiD) lenalidomide promotes myeloma cell death via Cereblon (CRBN)-dependent ubiquitylation and proteasome-dependent degradation of IKZF1 and IKZF3. Although IMiDs have been used as first-line drugs for MM, the overall survival of refractory MM patients remains poor and demands the identification of novel agents to potentiate the therapeutic effect of IMiDs. Using an unbiased screen based on mass spectrometry, we identified the Runt-related transcription factor 1 and 3 (RUNX1 and RUNX3) as interactors of IKZF1 and IKZF3. Interaction with RUNX1 and RUNX3 inhibits CRBN-dependent binding, ubiquitylation, and degradation of IKZF1 and IKZF3 upon lenalidomide treatment. Inhibition of RUNXs, via genetic ablation or a small molecule (AI-10-104), results in sensitization of myeloma cell lines and primary tumors to lenalidomide. Thus, RUNX inhibition represents a valuable therapeutic opportunity to potentiate IMiDs therapy for the treatment of multiple myeloma.

Non-small cell lung cancer (NSCLC) is still an unresolved source of tumor-related death internationally. Current studies have discovered that microRNAs (miRNAs) are associated with diverse cancers development, including NSCLC. Our paper focused on the functional character of miR-4286 in NSCLC. miR-4286 level in 68 cases of NSCLC tissues, matched neighboring nontumor tissues and different cancer cell lines were inspected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The connection concerning miR-4286 expression and clinicopathological features of patients with NSCLC were further determined. After knockdown or overexpression of miR-4286, cell viability, cell cycle, and/or apoptotic cells were examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assay, respectively. Moreover, the cell cycle- and apoptosis-related proteins were estimated by qRT-PCR and Western blot. In comparison with the matched nontumor tissues, miR-4286 was significantly enhanced in lung malignancy tissues and different cell lines. miR-4286 expression was related with the tumor-node-metastasis stage, lymphatic metastasis, and distant metastasis. Cell viability was ominously weakened by suppression of miR-4286 in A549 cells, whereas was statistically upregulated by overexpression of miR-4286 in NCI-H1299 cells. Additionally, we detected that suppression of miR-4286 tempted cell cycle arrest in G1 stage and fortified apoptosis in A549 cells. Runx3 was recognized as one target gene of miR-4286, and the impacts of suppression of miR-4286 on cell viability and apoptosis were through regulation of Runt-related transcription factor 3. Our study suggests that miR-4286 overexpression represents a tumor promoter role in NSCLC cells.