Knocking down Sterol regulatory element binding protein 2 (SREBF2) inhibits the Serine Protease 8 (PRSS8) /sodium channel epithelial 1alpha subunit (SCNN1A) axis to reduce the cell proliferation, migration and epithelial-mesenchymal transformation of ovarian cancer

Abstract

The pathogenesis of ovarian cancer (OC) is complex. Serine Protease 8 (PRSS8) is a potential biomarker for early detection of OC. Multiple databases were used to predict the expression of PRSS8, Sterol regulatory element binding protein (SREBP) and sodium channel epithelial 1alpha subunit (SCNN1A) in OC patients and to detect the relationship among the three. The expressions of PRSS8, SREBF2, SCNN1A and related factors of the pathway were detected by RT-qPCR and Western blot. The cell transfection was used to overexpress or inhibit the expression of PRSS8 and SREBF2, so as to explore its mechanism. MTT assay and Colony formation assay were used to detect cell proliferation. The Transwell and Wound Healing assays were utilized to measure cell invasion and migration. We have further confirmed cell-level studies in animals. We found that PRSS8 expression was up-regulated in OC patients and cell lines. Knocking down PRSS8 reduced the proliferation, migration and epithelial-mesenchymal transition (EMT) of OC cells, which was realized by SREBF2 transcriptional regulation. Knocking down SREBF2 reduced PRSS8 and then inhibited the expression of SCNN1A, thus affecting the proliferation, migration and EMT of OC cells. These results also applied to animals experiments. In conclusion, SREBF2 activates the PRSS8/SCNN1A axis to accelerate cell proliferation, migration and EMT of OC.

YTHDF2 protein stabilization by the deubiquitinase OTUB1 promotes prostate cancer cell proliferation via PRSS8 mRNA degradation

“…PRSS8 was previously suggested to be a candidate tumor suppressor ( 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ), but its role in prostate cancer remains unclarified. We compared the levels of PRSS8 in prostate cancer samples and paired normal samples with immunohistochemistry.…”

“…Loss of Prss8 in mice leads to lethality within 60 h after birth due to dehydration and dysfunctional skin ( 41 ), which was suggested to be independent of its protease activity ( 71 , 72 , 73 ). Besides, a potential role of PRSS8 in cancer was implicated by its loss of expression in several cancer types ( 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ). Loss of PRSS8 expression was partially attributed to DNA hypermethylation in bladder cancer, esophageal cancer, and breast cancer ( 50 , 74 , 75 ).…”

A Selective Histone Deacetylase Inhibitor Induces Autophagy and Cell Death via SCNN1A Downregulation in Glioblastoma Cells

“…Another study showed that SCNN1A upregulation by homeobox D9 (HOXD9) induced cell proliferation and migration in pancreatic cancer cells [ 52 ]. Cai et al demonstrated that inhibition of Serine Protease 8 (PRSS8)/SCNN1A by sterol regulatory element binding protein 2 (SREBF2) reduced the cell proliferation, migration, and epithelial–mesenchymal transformation of ovarian cancer [ 53 ]. Overexpression of SCNN1A was found in ovarian cancer tissues and cell lines, and higher expression was related to poor survival [ 54 ].…”

The role of Testis-Specific Protein Y-encoded-Like 2 in kidney injury

“…The chromatin immunoprecipitation (ChIP) assay was performed as previously described. 41 In short, the ChIP assay kit (Millipore, Darmstadt, Germany) was used according to the instructions provided. 90% Of the chromatin was diluted in ChIP dilatation buffer and incubated with 5 μL anti- SREBP-2 antibody or normal immunoglobulin (IgG).…”