3.3 Cancer
OPTN is also proved to be a tumor suppressor in cancer. Hu lab first found that OPTN is a tumor suppressor in lung cancer though a HACE1-OPTN axis. In detail, HACE1 could ubiquitylate on Lys193 of OPTN, which is a critical step in HACE1-activated autophagy, and form an autophagic complex with p62, accelerating the total cellular autophagic flux and facilitating in tumor suppression (Liu et al. , 2014). Recently, the Berger group analyzed an overview of the RNA-seq data provided by The Cancer Genome Atlas (TCGA) and found that high expression of the OPTN gene across several tumor types, especially in pancreatic cancer and renal cancer which was associated with the second and first highest OPTN expression of all tumor tissues respectively (Ali et al. , 2019). While they showed a weird phenomenon that OPTN knockdown has limited affect in the proliferation of three different human pancreatic cancer cell lines, Miapaca , BXPC3 and Suit2-007, significantly increased the migration in BXPC3 and Miapaca cells, but strikingly reduced the colony formation in all three cells. Autophagy is considered as a protective biological process in general. While, as for cancer, autophagy is not good for cancer cell, and kills cancer in the cradle (Nassour et al. , 2019). Considering that OPTN could induce autophagy and the Berger group’s ambiguous experimental results, we hold the opinion that OPTN is more tend to be a tumor suppressor.
3.4 Diabetic nephropathy
In addition, OPTN have antisenescence and protection effect in diabetic nephropathy though enhancing mitophagy. Diabetic nephropathy ((DN) is a complication of type 1 diabetes, most frequently and also devastatingly, and its diagnosis is traditionally based on microalbuminuria. As Kehonget al . find in clinical specimens, renal OPTN expression was negative correlation to tubulointerstitial injury scores. OPTN expression is also negatively correlated with serum creatinine level and positively correlated with the estimated glomerular filtration rate (eGFR), which is the indicator of DN. As these relationship turned out, OPTN is closely related to the progression of DN. Further study revealed an interesting result that the renal tubular cells that OPTN-positive ones always without expression senescence marker P16. What’s more, overexpression of OPTN increased mitophagosome formation and down regulated P16, P21, SA-β-gal, and SAHF which are features of cellular senescence and vice versa (Chen et al. , 2018). These study not only verified the role of OPTN in inducing autophagy when overexpression, but also reveal an new role of OPTN in antisenescence in diabetic nephropathy though mitophagy.