A frequent somatic mutation in CD274 3′-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding

Wang, Weipeng; Sun, Jing; Li, Fang; Li, Rui; Gu, Yuan; Liu, Cuiping; Peng, Yang; Zhu, Mingqing; Chen, Lüjun; Tian, Wenyan; Zhou, Huan; Mao, Yong; Zhang, Liang; Jiang, Jingting; Wu, Changping; Hua, Dong; Chen, Weichang; Lu, Binfeng; Ju, Jingfang; Zhang, Xueguang

doi:10.1002/humu.22014

Cited by 88 publications

(66 citation statements)

References 13 publications

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“…miRNAs are endogenous non-coding RNA of ~23 nucleotides, which inhibit protein translation by interacting with the 3′-untranslated regions (3′-UTRs) of the messenger RNAs (mRNAs) of target genes [17]. Although miRNAs have been increasingly described to be involved in the inhibition of B7/CD28 molecules [18–24], further investigations are needed to fully understand whether they participate in TGF-β1-mediated regulation of B7/CD28 molecules in colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4viathe miR-155/miR-143 axis

et al. 2016

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Transforming growth factor-beta 1 (TGF-β1) suppresses T cell function, promoting tumor immune escape. Yet, whether the depression of TGF-β1 on T cell function is mediated by co-inhibitory molecules B7-H3 and B7-H4 remains largely unclear. Here, we demonstrated that TGF-β1 elevated the expression of miR-155 in colorectal cancer cells through SMAD3 and SMAD4. The upregulated miR-155 attenuated miR-143 by inhibiting its direct target, the transcription factor CEBPB. Consequently, the direct target genes of miR-143, B7-H3 and B7-H4, were augmented in the cytoplasm and membrane of tumor cells. Over-expression of B7-H3 and B7-H4 in HCT-116 cells induced T cells to secrete TGF-β1 and the immunosuppressive cytokines IL-2, IL-6, and IL-17. Restoration of miR-143 inhibited the growth of HCT-116 xenograft tumors in mice, and also repressed the expression of B7-H3 and B7-H4 in the tumors. Thus, this study reveals the mechanism by which TGF-β1 leads to T cell-mediated tumor evasion through an increase in B7-H3 and B7-H4 expression.

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Section: Introductionmentioning

confidence: 99%

TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4viathe miR-155/miR-143 axis

et al. 2016

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“…It has been recently demonstrated that B7-H1 expression in cancer cells is regulated by miRNAs [16, 17]. To determine whether the HP-induced increase in B7-H1 expression in human gastric cancer cells occurs via miRNAs targeting B7-H1, we studied two candidate B7-H1 miRNAs (miR-152 and miR-200b) that were predicted byTargetScan and PicTar in AGS cells after HP infection.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, B7-H1 is an indicator of poor prognosis in patients with renal cell carcinoma [31], esophageal cancer [22], gastric carcinoma [7], breast cancer [32], ovarian cancer [33], bladder urothelial carcinoma [34], or pancreatic cancer [35]. It has been confirmed that the extent of B7-H1 expression in gastric cancer is significantly related to the clinicopathological features, including tumor size, depth of invasion, lymph node metastasis, and prognosis of patients [7, 17]. The results of our study demonstrated that B7-H1 expression in gastric cancer was associated with tumor malignancy; that is, the higher the expression of B7-H1, the lower the differentiation of the gastric cancer and the higher the TNM stage.…”

Section: Discussionmentioning

confidence: 99%

“…The downregulation of the expression of certain tumor-suppressive miRNAs can lead to the over-expression of target proteins, over-proliferation, the inhibition of cancer cell apoptosis and the acceleration of tumor development [15]. It has been reported that B7-H1 expression may be regulated by miR-570 in gastric cancer [16, 17] and by miR-20b, miR-21 and miR-130b in colorectal cancer [18]. Aberrant miRNA expression is involved in the development and progression of gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

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Helicobacter Pylori Promote B7-H1 Expression by Suppressing miR-152 and miR-200b in Gastric Cancer Cells

Xie

et al. 2017

PLoS ONE

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The most common cause of gastric cancer is infection with helicobacter pylori (HP), but the associated molecular mechanism is not well understood. In the present study, we found a marked increase in the expression of B7-H1, a member of the B7 co-stimulatory family of molecules that bind to programmed death-1 (PD-1) and play a critical immunoregulatory role in the cell-mediated immune response, in HP-positive gastric cancer tissue. Infection of cultured gastric cancer cells with HP promoted B7-H1 expression and inhibited miR-152 and miR-200b expression. We further demonstrated that these two miRNAs targeted B7-H1 mRNA and suppressed B7-H1 expression in gastric cancer cells. Finally, B7-H1 expression was found to correlate with miR-152 and miR-200b levels in gastric tumor tissues from human patients. Our findings suggest a novel mechanism by which HP infection promotes gastric cancer and also suggest potential targets, i.e., miR-152 and miR-200b, for the prevention and treatment of gastric cancer.

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“…CDCA7L interacts with c-Myc in bringing about cellular transformation in medulloblastoma [37]. Mutation of CD274 leading to its overexpression have been associated with gastric carcinoma [38]. Apart from these, mutations in ODZ1, TTN and EP300 are already reported in cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Somatic Variations in Cervical Cancers in Indian Patients

Das

Bansal

Rao³

et al. 2016

PLoS ONE

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There are very few reports that describe the mutational landscape of cervical cancer, one of the leading cancers in Indian women. The aim of the present study was to investigate the somatic mutations that occur in cervical cancer. Whole exome sequencing of 10 treatment naïve tumour biopsies with matched blood samples, from a cohort of Indian patients with locally advanced disease, was performed. The data revealed missense mutations across 1282 genes, out of 1831 genes harbouring somatic mutations. These missense mutations (nonsynonymous + stop-gained) when compared with pre-existing mutations in the COSMIC database showed that 272 mutations in 250 genes were already reported although from cancers other than cervical cancer. More than 1000 novel somatic variations were obtained in matched tumour samples. Pathways / genes that are frequently mutated in various other cancers were found to be mutated in cervical cancers. A significant enrichment of somatic mutations in the MAPK pathway was observed, some of which could be potentially targetable. This is the first report of whole exome sequencing of well annotated cervical cancer samples from Indian women and helps identify trends in mutation profiles that are found in an Indian cohort of cervical cancer.

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A frequent somatic mutation in CD274 3′-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding

Cited by 88 publications

References 13 publications

TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4viathe miR-155/miR-143 axis

TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4viathe miR-155/miR-143 axis

Helicobacter Pylori Promote B7-H1 Expression by Suppressing miR-152 and miR-200b in Gastric Cancer Cells

Somatic Variations in Cervical Cancers in Indian Patients

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