HuR confers IL-17a-induced migration and invasion of gastric cancer cells via upregulation of Snail translation

Human antigen R affects the migration and invasion of human lung cancer A549 cells and regulates E-cadherin suppressor Snail

“…Accordingly, the observed downregulation of E-cadherin expression might not be the direct consequence of HuR overexpression, but likely via an E-cadherin repressor upregulated by HuR. In human gastric cancer AGS cells, an increased level of HuR was associated with promoted Snail translation, leading to reduced E-cadherin expression and enhanced EMT, while these effects were reversed in HuR knockdown cells (19). Similarly, HuR was shown to directly interact with the 3'-UTR of the Snail mRNA, stabilizing Snail expression and promoting EMT in pancreatic cancer MIA PaCa-2 cells (20).…”

“…The progression of cancer and the effectiveness of metastasis are tightly associated with EMT, in which E-cadherin downregulation and N-cadherin upregulation play an essential role due to their primary function in maintaining the epithelial cell-to-cell interactions. In gastric cancer cell lines, interleukin (IL)-17a and methyltransferase-like 3 were shown to promote EMT and repress E-cadherin expression via HuR pathway (19,44). In human colorectal adenocarcinoma Caco-2 cells, HuR overexpression was shown to prevent CUG-binding protein 1-induced E-cadherin repression, while HuR deletion was found to increase the miR-675 level, which in turn suppressed the expression of E-cadherin (17,18).…”

“…In addition, HuR was demonstrated to influence the expression of E-cadherin in esophageal squamous cell carcinoma and human colon carcinoma cells (16)(17)(18). As an RNA stabilizing protein, HuR was also shown to impact on Snail expressions in gastric cancer and pancreatic cancer cells (19,20). However, whether HuR could directly stabilize Snail to affect EMT marker expression in lung cancer cells is currently not documented.…”

IL-17A promotes Helicobacter pylori-induced gastric carcinogenesis via interactions with IL-17RC

“…Several human clinical studies have established a relationship between the expression of IL-17A and GC progression. Upregulation of IL-17A is observed in serum and tumor samples of GC patients compared to healthy controls [ 17 – 21 ]. In the present study, IL-17A protein was detectable in the surface mucous epithelium and gastric glands of a normal WT mouse stomach.…”

“…However, studies to date on the role of IL-17A in GC development have generated inconsistent findings. For instance, IL-17A has been shown to promote tumor growth by stimulating angiogenesis and invasive capacity of tumor cells along with inhibiting apoptosis [20][21][22]. In contrast, infiltration of intratumoral IL-17A-producing cells is correlated with antitumor immune contexture and improved response to adjuvant chemotherapy in GC [15].…”