57214

CEMIP

KIAA1199 is a gene included in the Human Unidentified Gene-Encoded (HUGE) large protein database which contains more than 2,400 members identified in the Kazusa cDNA sequencing project. Early studies described KIAA1199 as an inner ear-specific protein in which 3 point mutations were found to be associated with nonsyndromic hearing loss. Recently, KIAA1199 has been found to play a central role in hyaluronan binding and depolymerisation, and a small number of studies indicate its senescence/apoptosis-promoting role. An increasing body of evidence suggests its involvement in cancer progression, metastasis and poor prognosis of patients with cancer as determined in clinical studies. It has also been shown, in vitro, that KIAA1199 influences the proliferation, adhesion, motility, invasiveness and epithelial-to-mesenchymal transition of cancer cells. pathway signalling analysis found that KIAA1199 is a likely target gene of the Wnt/beta-catenin signalling pathway. Therefore, KIAA1199 may be a new and prospective target for cancer therapy, although further in vitro and in vivo investigations are required.

BACKGROUND: KIAA1199 was upregulated in diverse cancers, but the association of KIAA1199 with gastric cancer (GC), the biological role of KIAA1199 in GC cells and the related molecular mechanisms remain to be elucidated. METHODS: KIAA1199 expression was analysed by reverse transcription-polymerase chain reaction assay (RT-PCR) and immunohistochemistry (IHC) in GC patient tissue. The small hairpin RNA (shRNA) was applied for the knockdown of endogenous KIAA1199 in NCI-N87 and AGS cells. MTT, colony formation, scratch wounding migration, transwell chamber migration and invasion assays were employed respectively to investigate the role of KIAA1199 in GC cells. The potential signaling pathway of KIAA1199 induced migration and invasion was detected. RESULTS: KIAA1199 was upregulated in GC tissue and was an essential independent marker for poor prognosis. Knockdown KIAA1199 suppressed the proliferation, migration and invasion in GC cells. KIAA1199 stimulated the Wnt/beta-catenin signaling pathway and the enzymatic activity of matrix metalloproteinase (MMP) family members and thus accelerated the epithelial-to-mesenchymal transition (EMT) progression in GC cells. CONCLUSION: These findings demonstrated that KIAA1199 was upregulated in GC tissue and associated with worse clinical outcomes in GC, and KIAA1199 acted as an oncogene by promoting migration and invasion through the enhancement of Wnt/beta-catenin signaling pathway and MMPs mediated EMT progression in GC cells.

BACKGROUND: LncRNA TUG1 has been reported to be highly expressed in CRC samples and cells and promoted metastasis by affecting EMT, indicating a poor prognosis for colorectal cancer (CRC). In this study, we determined the underlying mechanism for tumor oncogenesis of lncRNA TUG1 in CRC metastasis. METHODS: The expressions of miR-600 and KIAA1199 in 76 CRC patients and CRC cells and CRC metastatic tissues were determined using qRT-PCR. epithelial-mesenchymal transition (EMT)-related proteins were determined using western blot. CRC cell metastasis was assessed by colony formation, wound healing and transwell assay. Luciferase reporter gene assay was used to confirm miR-600 binding to KIAA1199 3'UTR. RESULTS: Our data showed that lncRNA TUG1 was upregulated in CRC cells, miR-600 was downregulated in CRC tissues, cell lines and CRC metastatic tissues, and low miR-600 expression predicted a poor clinical prognosis. Overexpression of miR-600 suppressed CRC cell migration/invasion and EMT-related proteins in vitro, inhibited tumor volume and weight, and decreased the number of CRC liver metastasis in vivo. KIAA1199 was upregulated in CRC tissues, and was negatively regulated by miR-600. KIAA1199 overexpression promoted CRC cell migration and invasion, which reversed the inhibition effect of miR-600 mimic on migration and invasion of CRC cells. Moreover, TUG1 negatively regulated miR-600, and inhibition of TUG1 suppressed CRC cell migration and invasion and EMT-related proteins via regulating miR-600. CONCLUSION: Our study proved that TUG1 promoted KIAA1199 expression to accelerate EMT and metastasis of CRC cell through inhibition of miR-600 expression.