Zinc Finger Protein 36L1 (ZFP36L1): Gene Expression, Regulation and Interactions with Immune Receptors in Human Tumour Cells.

The Zinc finger protein 36 like 1 (ZFP36L1) or Butyrate response factor 1 (BRF1) is involved in the differentiation, proliferation, and angiogenesis of various cell types. ZFP36L1 can positively or negatively regulate cellular processes such as transcription and signalling, depending on external and internal stimulations. The basic mechanism with which this protein functions is via its binding to the AU- rich regions of the mRNA causing their degradation. However, its exact roles in cellular physiology and mRNA targets are poorly understood. We hypothesize that ZFP36L1 regulates expression of effectors and receptors linked to immunity and is therefore important in controlling cell proliferation and cancer. We investigated roles of ZFP36L1 in regulating expression of TNF α and VEGF A as well as of the adhesion receptor CD44 involved in lymphocyte activation, haematopoiesis and tumour metastasis. In this study we also report data on the detection and quantification of ZFP36L1 in several tumour cell lines such as THP1, Jurkat, B16, MCF7, and MC38. To study the function of ZFP36L1 a CRISPR-Cas9 system was used to generate ZFP36L1 knockout MC38 cell line. Our results show that ZFP36L1 limits production of TNF α and VEGF A. Our preliminary data also show co-localization of ZFP36L1 with CD44 upon cellular permeablization, which needs further investigation and future studies. In conclusion, we show that ZFP36L1 is expressed in various cancer cell lines including Jurkat immune cells and its expression regulates various effector molecules and cell growth.