TNFAIP8 promotes the migration of clear cell renal cell carcinoma by regulating the EMT

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by high metastatic potential, and the epithelial-mesenchymal transition (EMT) has been shown to play a key role in multiple cancer progression, migration and metastasis and is the leading cause of poor prognosis. Currently, tumor necrosis factor-α-induced protein 8 (TNFAIP8/TIPE) is a newly discovered tumorigenesis factor, and TNFAIP8 and the EMT influence the migration of renal cancer cells. Methods: In this study, we first analyzed the relationship between TNFAIP8 and ccRCC using bioinformatics, followed by immunohistochemistry to evaluate the relationship between the two in clinical samples. Subsequently, reverse transcription PCR and western blotting confirmed the expression of TNFAIP8 in ccRCC cells. Furthermore, we measured the migration and invasion abilities by using wound healing and transwell assays after overexpression or knockdown of TNFAIP8 in cells. In addition, we verified whether TNFAIP8 affects the EMT process in ccRCC by quantitative real-time PCR, western blotting, immunohistochemistry and immunofluorescence experiments. Results: Through database analysis, we found that TNFAIP8 was highly expressed in ccRCC patients and was positively correlated with tumor stage and grade, indicating that TNFAIP8 is associated with the development of advanced ccRCC and poor prognosis. We subsequently confirmed that TNFAIP8 was abnormally overexpressed in clinical samples and ccRCC cell lines and that TNFAIP8 promoted ccRCC cell migration and invasion in vitro. Finally, we found that TNFAIP8 regulated EMT-related molecule expression and regulated the EMT process. Conclusion: High expression of TNFAIP8 reinforces migration and regulates the EMT in ccRCC, conferring the metastatic potential of ccRCC and suggesting that TNFAIP8 may be a potential therapeutic target for the treatment of advanced ccRCC.

Current research status of TNFAIP8 in tumours and other inflammatory conditions (Review)

“…TNFAIP8 is a prognostic marker for tumours. Elevated expression of TNFAIP8 was found in patients with different cancer types, such as NSCLC (31), colon cancer (32), GC (33), epithelial ovarian cancer (EOC) (34), endometrial cancer (EC) (35), invasive ductal breast carcinoma (36), oesophageal squamous cell carcinoma (37), pN0 oesophageal squamous cell carcinoma (38), hepatocellular carcinoma (HCC) (39), diffuse large B-cell lymphoma (DLBCL) (40), clear cell renal cell carcinoma (ccRCC) (41) and papillary thyroid carcinoma (30), which are often significantly associated with poor prognostic features; for example, advanced tumour stage, lymph node metastasis, increased histological grade, poor survival time and tumour recurrence, thus implying its potential diagnostic and prognostic value.…”

Long non-coding RNA ARAP1-AS1 contributes to cell proliferation and migration in clear cell renal cell carcinoma via the miR-361-3p/placental growth factor axis

“…Cell migration was assessed using a wound healing assay, as previously described [ 37 ]. After transfection, 2 × 10 6 cells were seeded in 6-well plates and incubated until 90% confluence.…”

A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma

“…For example, Chen JY et al identified 14 potential biomarkers for predicting tumorigenesis and progression of ccRCC using weighted gene co-expression network analysis ( 14 ). Zhong MY et al indicated that tumor necrosis factor-α-induced protein 8 (TNFAIP8) was highly expressed in ccRCC patients and was associated with the development of advanced ccRCC and poor prognosis by database analysis ( 15 ). Bioinformatics analysis of the profiling data by Ni D et al identified FOXO3a as a key factor in ccRCC metastasis ( 16 ).…”