Panoply™ Human MERTK Knockdown Stable Cell Line

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) are unable to receive standard salvage therapy; therefore, there is an urgent need to explore new therapeutic targets for DLBCL. Here, researchers for the first time discovered that the proto-oncogene MerTK is abnormally highly expressed in DLBCL samples and cell lines. Targeting and knocking down MerTK or applying the MerTK small molecule inhibitor UNC2025 inhibited DLBCL cell proliferation, promoted apoptosis, and suppressed G2/M phase arrest. Transcriptome sequencing after targeted knockdown of MerTK and subsequent Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed significant enrichment of differentially expressed genes involved in the autophagy pathway, with significantly upregulated expression of ANXA1. Further studies showed that targeted knockdown of MerTK inhibited autophagic flux by increasing the expression of ANXA1 in DLBCL cells. Overexpression of ANXA1 reduced the proliferation and autophagic flux of DLBCL cells. In an in vivo mouse xenograft DLBCL model, targeted knockdown of MerTK reduced disease progression. UNC2025 inhibited tumor growth in a DLBCL cell-derived xenograft model. Therefore, MerTK is abnormally expressed in DLBCL, and targeted inhibition of MerTK can inhibit DLBCL growth in vitro and in vivo. This study provides clues for precision therapy targeting MerTK in DLBCL.

Here, researchers constructed MerTK knockdown U2932 and OCI-LY7 cells (Figure 1A). In cell proliferation experiments, compared with control cells, the survival rate of MerTK knockdown U2932 or OCI-LY7 cells was significantly reduced at 72 to 96 hours (Figure 1B). Cell invasion ability was assessed using Matrigel-coated Transwell chambers. The results showed that the invasion ability of MerTK knockdown U2932 and OCI-LY7 cells was significantly reduced by 47.9% and 33.3%, respectively, compared with control cells (Figure 1C). Western blot analysis showed that the expression levels of phosphorylated AKT (p-AKT) and phosphorylated ERK1/2 (p-ERK1/2) were significantly reduced in MerTK knockdown U2932 and OCI-LY7 cells compared with control cells (Figure 1D).

Figure 1. MerTK inhibition by shRNA suppressed proliferation, invasion and activation of downstream signaling. (Li Y, et al., 2025)