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Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.

ABSTRACT: Recent evidence shows the emerging roles of intelectin 1 (ITLN1), a secretory lectin, in human cancers. Our previous studies have implicated the potential roles of ITLN1 in the aggressiveness of gastric cancer. Herein, we investigated the functions, downstream targets, and clinical significance of ITLN1 in the progression of gastric cancer. We demonstrated that ITLN1 increased the levels of hepatocyte nuclear factor 4 alpha (HNF4?), resulting in suppression of nuclear translocation and transcriptional activity of ?-catenin in gastric cancer cells. Mechanistically, ITLN1 attenuated the activity of nuclear factor-kappa B, a transcription factor repressing the HNF4? expression, in gastric cancer cells through inactivating the phosphoinositide 3-kinase/AKT/Ikappa B kinase signaling. Gain- and loss-of-function studies demonstrated that ITLN1 suppressed the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. In addition, restoration of HNF4? expression prevented the gastric cancer cells from ITLN1-mediated changes in these biological features. In clinical gastric cancer tissues, HNF4? expression was positively correlated with that of ITLN1. Patients with high ITLN1 or HNF4? expression had greater survival probability. Taken together, these data indicate that ITLN1 suppresses the progression of gastric cancer through up-regulation of HNF4?, and is associated with improved survival in patients with gastric cancer.

SUBMITTER: Li D

PROVIDER: S-EPMC4599263 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.

Li Dan D Zhao Xiang X Xiao Yong Y Mei Hong H Pu Jiarui J Xiang Xuan X Jiao Wanju W Song Huajie H Qu Hongxia H Huang Kai K Zheng Liduan L Tong Qiangsong Q

Oncotarget 20150601 18

Recent evidence shows the emerging roles of intelectin 1 (ITLN1), a secretory lectin, in human cancers. Our previous studies have implicated the potential roles of ITLN1 in the aggressiveness of gastric cancer. Herein, we investigated the functions, downstream targets, and clinical significance of ITLN1 in the progression of gastric cancer. We demonstrated that ITLN1 increased the levels of hepatocyte nuclear factor 4 alpha (HNF4α), resulting in suppression of nuclear translocation and transcrip ...[more]

PMID: 25965823

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Project description:BackgroundRetinoic acid induced 14 (RAI14), also known as NORPEG, is reported as being deregulated in non-small-cell lung cancer, together with having involvement in its cell proliferation as a super enhancer related gene.PurposeThe objective of this study was to investigate the role of RAI14 in the progression and metastasis of gastric cancer and explore the associated mechanism.Materials and methodsGEPIA database was used to analyze the expression of RAI14 in gastric cancer. MNK45 and AGS cells were transfected with siRNA-RAI14 to block the expression of RAI14. Cell Counting Kit 8 and colony formation assays were performed to measure cell proliferation. Cell migration and invasion capacities was examined by transwell assay. Apoptosis rate was detected using flow cytometry, and the protein levels of apoptosis-related proteins was determined using Western blot assay. Reverse-transcription PCR assay was used to detect the expressions of RAB31.ResultsGene expression profiling interactive analysis revealed that RAI14 was substantially upregu-lated in gastric cancer and higher expression of RAI14 was associated with worse prognosis. We also observed that the knockdown of RAI14 by siRNA-RAI14 transfection suppressed growth capacity of MKN45 and AGS cells. Also, RAI14 knockdown inhibited migration and invasion of MKN45 and AGS cells in vitro. Moreover, RAI14 knockdown was observed to accelerate cell apoptosis via down-regulation of Bcl-2 and upregulation of Bax in MKN45 and AGS cells. Furthermore, downregulation of RAI14 inhibited the activation of Akt pathway, and activation of Akt by IGF-1 could restore the reduced proliferation induced by RAI14 knockdown. In addition, we found that RAI14 had a positive correlation with the RAB31 in gastric cancer by GEPIA reverse-transcription PCR and Western blot assays, and the reduced proliferation caused by RAI14 knockdown was restored by RAB31.ConclusionRAI14 knockdown inhibited proliferation, migration and invasion and promoted apoptosis by downregulating the Akt pathway in gastric cancer cells, and RAB31 might be a downstream target gene of RAI14, providing a novel sight into the molecular mechanism of RAI14 and a potential target for gastric cancer treatment.

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Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.

Publications

Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.

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