TGFB2 serves as a link between epithelial-mesenchymal transition and tumor mutation burden in gastric cancer

Yang, Bowen; Bai, Jing; Shi, Ruichuan; Shao, Xinye; Yang, Yujing; Jin, Yue; Che, Xiaofang; Zhang, Ye; Qu, Xiujuan; Liu, Yunpeng; Li, Zhi

doi:10.1016/j.intimp.2020.106532

Cited by 26 publications

(23 citation statements)

References 31 publications

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“…TGFB2 is a hallmark in various malignant tumors, and treatment of cancer based on the specific inhibition of TGFB2 is currently being developed (17). The mode of action, effectuality and tolerability in vitro and in vivo of Trabedersen (AP-12009), an antisense oligodeoxynucleotide inhibitor targeting TGFB2, has been confirmed (47).…”

Section: Discussionmentioning

confidence: 99%

“…EMT and tumor mutation burden in gastric cancer (17). EMT is a key biological process that induces malignant tumor cell migration and invasion (20,21).…”

Section: Mir-454-3p Inhibits Non-small Cell Lung Cancer Cell Proliferation and Metastasis By Targeting Tgfb2mentioning

confidence: 99%

“…Transforming growth factor-β2 (TGFB2) is a protein coding gene of TGF-β2, and it has been revealed to regulate tumor cell growth, proliferation and metastasis (16,17). Emerging evidence has revealed that TGF-β2 was upregulated in numerous types of cancer (18).…”

Section: Introductionmentioning

confidence: 99%

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miR‑454‑3p inhibits non‑small cell lung cancer cell proliferation and metastasis by targeting TGFB2

Liao

Liang

Kang³

et al. 2021

Oncol Rep

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Accumulating studies have suggested that microRNAs (miRs) play a significant role in lung cancer development and progression, especially in non-small cell lung cancer (NSCLC). The present study aimed to investigate the associations between miR-454-3p and NSCLC progression. qPCR assay was applied to examine the expression of miR-454-3p and transforming growth factor-β2 (TGFB2) in tissues and cell lines. CCK-8 and EdU assays were used to detect cell proliferation. Wound-healing and Transwell assays were conducted to assess cell migration and invasion. Western blotting assay was performed to explore the protein levels of epithelial-mesenchymal transition (EMT) markers. The interaction between miR-454-3p and TGFB2 was investigated with a luciferase reporter assay. miR-454-3p was downregulated in NSCLC tissues and NSCLC cell lines. miR-454-3p overexpression led to the suppression of proliferation, migration, and invasion in A549 and NCI-H1650 cells. In addition, the overexpression of miR-454-3p in A549 and NCI-H1650 cells significantly inhibited EMT. TGFB2 was revealed to be a direct target of miR-454-3p by using TargetScan database and luciferase reporter assay. TGFB2 was observed to be upregulated in NSCLC tissues and cell lines. Further mechanistic studies revealed that the inhibitory effects of miR-454-3p on NSCLC were reversed upon overexpression of TGFB2. These findings provided strong evidence that miR-454-3p suppressed NSCLC cell proliferation and metastasis by targeting TGFB2. The study suggests that targeting miR-454-3p could be a promising strategy for treating NSCLC.

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Section: Discussionmentioning

confidence: 99%

“…EMT and tumor mutation burden in gastric cancer (17). EMT is a key biological process that induces malignant tumor cell migration and invasion (20,21).…”

Section: Mir-454-3p Inhibits Non-small Cell Lung Cancer Cell Proliferation and Metastasis By Targeting Tgfb2mentioning

confidence: 99%

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miR‑454‑3p inhibits non‑small cell lung cancer cell proliferation and metastasis by targeting TGFB2

Liao

Liang

Kang³

et al. 2021

Oncol Rep

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“…For gliomas, Arslan et al [ 46 ] showed that TGFβ2 could trigger the malignant phenotype of high-grade gliomas by inducing migration, and Zhang et al [ 47 ] reported that there exited a potential mechanism of autophagy-associated glioma invasion that TGFβ2 could initiate autophagy via Smad and non-Smad pathway to promote glioma cells’ invasion. In gastric cancer, Yang et al demonstrated that TGFβ2 played a vital role in linking epithelial–mesenchymal transition and tumor mutational burden, which suggested that TGFβ2 may be a predictive therapeutic target for GC [ 48 ]. Wang et al [ 49 ] showed that the tumor-associated macrophages participated in GC cell invasion and metastasis through the TGFβ2/ nuclear factor kappa B /Kindlin-2 axis, providing a possibility for new treatment options and approaches.…”

Section: Discussionmentioning

confidence: 99%

Identification of the subtypes of gastric cancer based on DNA methylation and the prediction of prognosis

Chen

et al. 2020

Clin Epigenet

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Background Gastric cancer (GC) is a digestive system cancer with a high mortality rate globally. Previous experiences and studies have provided clinicians with ample evidence to diagnose and treat patients with reasonable therapeutic options. However, there remains a need for sensitive biomarkers that can provide clues for early diagnosis and prognosis assessment. Results We found 610 independent prognosis-related 5′-cytosine-phosphate-guanine-3′ (CpG) sites (P < 0.05) among 21,121 sites in the training samples. We divided the GC samples into seven clusters based on the selected 610 sites. Cluster 6 had relatively higher methylation levels and high survival rates than the other six clusters. A prognostic risk model was constructed using the significantly altered CpG sites in cluster 6 (P < 0.05). This model could distinguish high-risk GC patients from low-risk groups efficiently with the area under the receiver operating characteristic curve of 0.92. Risk assessment showed that the high-risk patients had poorer prognosis than the low-risk patients. The methylation levels of the selected sites in the established model decreased as the risk scores increased. This model had been validated in testing group and its effectiveness was confirmed. Corresponding genes of the independent prognosis-associated CpGs were identified, they were enriched in several pathways such as pathways in cancer and gastric cancer. Among all of the genes, the transcript level of transforming growth factor β2 (TGFβ2) was changed in different tumor stages, T categories, grades, and patients’ survival states, and up-regulated in patients with GC compared with the normal. It was included in the pathways as pathways in cancer, hepatocellular carcinoma or gastric cancer. The methylation site located on the promoter of TGFβ2 was cg11976166. Conclusions This is the first study to separate GC into different molecular subtypes based on the CpG sites using a large number of samples. We constructed an effective prognosis risk model that can identify high-risk GC patients. The key CpGs sites or their corresponding genes such as TGFβ2 identified in this research can provide new clues that will enable gastroenterologists to make diagnosis or personalized prognosis assessments and better understand this disease.

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“…Overexpression of TGFB2 has been reported to be positively associated with EMT status and negatively with TMB levels in GC. It affects TMB levels by regulating the DNA damage repair pathways and immune infiltrates, thus suggesting that detection of TGFB2 expression may predict response to ICIs in GC patients [ 175 ]. Furthermore, immune checkpoint inhibitors have been used to treat advanced GCs carrying high-frequency microsatellite instability (MSI-H) or mismatch repair defects (dMMR).…”

Section: Immunotherapies: Novel Insights and Advancesmentioning

confidence: 99%

From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers—A Multidisciplinary Perspective

Accordino

Lettieri

Bortolotto

et al. 2020

Cancers

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Despite the progress during the last decade, patients with advanced gastric and esophageal cancers still have poor prognosis. Finding optimal therapeutic strategies represents an unmet need in this field. Several prognostic and predictive factors have been evaluated and may guide clinicians in choosing a tailored treatment. Data from large studies investigating the role of immunotherapy in gastrointestinal cancers are promising but further investigations are necessary to better select those patients who can mostly benefit from these novel therapies. This review will focus on the treatment of metastatic esophageal and gastric cancer. We will review the standard of care and the role of novel therapies such as immunotherapies and CAR-T. Moreover, we will focus on the analysis of potential predictive biomarkers such as Modify as: Microsatellite Instability (MSI) and PD-L1, which may lead to treatment personalization and improved treatment outcomes. A multidisciplinary point of view is mandatory to generate an integrated approach to properly exploit these novel antiproliferative agents.

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TGFB2 serves as a link between epithelial-mesenchymal transition and tumor mutation burden in gastric cancer

Cited by 26 publications

References 31 publications

miR‑454‑3p inhibits non‑small cell lung cancer cell proliferation and metastasis by targeting TGFB2

miR‑454‑3p inhibits non‑small cell lung cancer cell proliferation and metastasis by targeting TGFB2

Identification of the subtypes of gastric cancer based on DNA methylation and the prediction of prognosis

From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers—A Multidisciplinary Perspective

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