Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy

Han, Yang; Jia, Chengyou; Cong, Xianling; Yu, Fei; Cai, Haidong; Fang, Shuai; Cai, Li; Yang, Haojie; Sun, Yutong; Li, Dan; Liu, Jin; Xie, Ruting; Yuan, Xueyu; Zhong, Xiaoming; Li, Ming; Wei, Qing; Lv, Zhongwei; Fu, Da; Ma, Yu‐Shui

doi:10.1371/journal.pone.0134682

Cited by 13 publications

(15 citation statements)

References 42 publications

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“…However, the other research showed that TGFbR2 acted as a proto-oncogene; its expression was dramatically increased in non-small-cell lung cancer tissues compared with non-neoplastic tissues, and overexpression of TGFbR2 was a significant risk factor for decreased overall survival and disease-free survival in non-small-cell lung cancer patients. 30 The inconsistent expression of miR-155 and TGFbR2 might be explained by the differences in tumor classification, tumor staging, or immune functions. We should further address the biological functions of miR-155 and TGFbR2 in GC in future studies.…”

Section: In Vivo Role Of Mir-155 and Tgfbr2 In Gastric Cancermentioning

confidence: 99%

MicroRNA‐155 promotes gastric cancer growth and invasion by negatively regulating transforming growth factor‐β receptor 2

Zhang

Sun

et al. 2018

Cancer Science

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Gastric cancer (GC) is one of the most common malignancies worldwide and has high morbidity and mortality rates. It is essential to elucidate the molecular events of GC proliferation and invasion, which will provide new therapeutic targets for GC. The inactivation of transforming growth factor‐β receptor 2 (TGFβR2) correlates with cancer cell growth and metastasis, but the mechanisms underlying the downregulation of TGFβR2 expression remain unknown. MicroRNAs (miRNAs) act as post‐transcriptional regulators and play a key role in the development of cancers. Bioinformatics analysis and luciferase reporter assays have shown that miR‐155 directly binds to the 3′‐UTR of TGFβR2 mRNA. In this study, we found that the TGFβR2 protein levels, but not mRNA levels, were downregulated in GC tissues, and the levels of miR‐155 were significantly increased in GC tissues. We deduced that miR‐155 was inversely correlated with TGFβR2 in GC cells. In vitro studies showed that overexpression of miR‐155 in SGC7901 inhibited the expression of TGFβR2 and then promoted GC cell proliferation and migration, whereas miR‐155 inhibitor showed opposite effects. In addition, the tumor‐suppressing function of TGFβR2 was verified by using siRNA and TGFβR2 overexpressing plasmids. The results showed that miR‐155 promotes cell growth and migration by negatively regulating TGFβR2. Thus, miR‐155‐regulated TGFβR2 as a potential therapeutic target in GC.

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Section: In Vivo Role Of Mir-155 and Tgfbr2 In Gastric Cancermentioning

confidence: 99%

MicroRNA‐155 promotes gastric cancer growth and invasion by negatively regulating transforming growth factor‐β receptor 2

Zhang

Sun

et al. 2018

Cancer Science

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“…Low levels of TGFβR2 proteins were negatively correlated with poor survival in patients with nasopharyngeal carcinoma [13]. However, some researchers found that TGFβR2 as a proto-oncogene, the expression was significantly higher in NSCLC tissues than in non-neoplastic tissues, and high expression of TGFβR2 was a critical risk factor for reduced survival in NSCLC patients [7]. And in subsequently vitro experiments, TGFβR2 could promote malignant characteristics in A549 [28] and H1299 cells [29].…”

Section: Discussionmentioning

confidence: 99%

“…The blockade of TGFβ signaling is always through either interrupt of TGFβ responses or the development of genetic alterations and epigenetic modifications in its components especially TGFβR2 [11]. As a tumor-suppressor gene, TGFβR2 is down-regulated in multiple cancer types [7, 12–14]. Then cancer cells lose their sensitivity to TGFβ-mediated growth inhibitory effect due to TGFβR2 down-regulation [15].…”

Section: Introductionmentioning

confidence: 99%

Onco-miR-130 promotes cell proliferation and migration by targeting TGFβR2 in gastric cancer

Duan

Zhang

et al. 2016

Oncotarget

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MicroRNAs (miRNAs) have been proved to play crucial roles in tumorigenesis. TGFβ signal pathway abnormality is found in various cancers and correlates with tumor proliferation and metastasis. However, the mechanisms underlying the dys-regulation of TGFβR2 expression in GC have not been investigated yet. In this study, we found that the TGFβR2 protein was clearly repressed in tumor tissues, while miR-130 expression level was dramatically increased in GC tissues. Firefly luciferase activity assay revealed that miR-130 could directly bind to 3′UTR of TGFβR2 mRNA. Meanwhile, miR-130 mimics lead to the decreased TGFβR2 protein levels, while miR-130 inhibitors enhanced TGFβR2 expression in SGC7901 cells. Subsequent functional experiments showed that overexpressed miR-130 could promote proliferation and migration of SGC7901 cells. And siRNA-mediated TGFβR2 down-regulation could simulate the effects of miR-130 mimics on phenotypes of SGC7901 cells. Furthermore, there existed intense relationship between the expression level of miR-130 and epithelial-mesenchymal markers. Our results demonstrated that miR-130 was an oncogene by directly targeting TGFβR2 in GC.

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“…Triller et al (67) observed a significant negative correlation between MRP1 expression and a more favorable response rate to chemotherapy in patients with NSCLC. Similarly, it is worth noting that increased expression of ABCG4 and transforming growth factor β receptor type 2 are also identified as novel poor prognostic factors of chemotherapy in NSCLC patients (68,69). It is possible that an increase in MRP1-mediated efflux of anti-neoplastic agents reduces the intracellular concentration, and thereby decreases the therapeutic efficacy of the agents.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of the multidrug resistance‑associated protein�1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

Wong

Zhou

et al. 2018

Oncol Rep

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The multidrug resistance‑associated protein 1 (MRP1) gene has been found to be consistently overexpressed in the majority of patients with non‑small cell lung cancer (NSCLC). MRP1 is known for its ability to actively decrease intracellular drug concentration, limiting the efficacy of cancer chemotherapy; however, data on the clinical relevance of MRP1 is inconclusive. In the present meta‑analysis, all available published data were combined to provide an updated view on the clinicopathological relevance of MRP1 in patients with NSCLC. A systematic search was conducted to obtain relevant studies published in English, Chinese and Japanese databases. All data from patients with NSCLC who underwent testing for MRP1, by either immunohistochemistry or reverse transcription‑polymerase chain reaction, were extracted and combined for further analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each selected study, with either the fixed‑effects model or the random‑effects model where appropriate. The quality of methodology, heterogeneities and publication bias of the included articles were also analyzed. A total of 36 clinical studies involving 3,278 patients were included in the study. It was found that the increased expression of the MRP1 gene was associated with the following subgroups of patients: Non‑smokers vs. smokers (OR, 2.54; 95% CI, 1.17‑5.54; P=0.019); adenocarcinoma vs. squamous cell carcinoma (OR, 1.58; 95% CI, 1.16‑2.17; P=0.004); clinical stage III‑IV vs. stage I‑II (OR, 1.36; 95% CI, 1.11‑1.66; P=0.003); lymph node metastases (OR, 1.32; 95% CI, 1.09‑1.61; P=0.005); poor response to chemotherapy (OR, 0.41; 95% CI, 0.23‑0.72; P=0.002) and reduced 3‑year survival rate (OR, 0.40; 95% CI, 0.23‑0.68; P=0.001). In conclusion, the findings from this study suggest that increase in MRP1 gene expression is associated with being a non‑smoker, adenocarcinoma, advanced clinical stages and a poor response to chemotherapy in patients with NSCLC. The results from the most extensive and updated data on MRP1 support the requirement for continued investigation into the potential use of MRP1 as a biomarker/clinical indicator for NSCLC.

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Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy

Cited by 13 publications

References 42 publications

MicroRNA‐155 promotes gastric cancer growth and invasion by negatively regulating transforming growth factor‐β receptor 2

MicroRNA‐155 promotes gastric cancer growth and invasion by negatively regulating transforming growth factor‐β receptor 2

Onco-miR-130 promotes cell proliferation and migration by targeting TGFβR2 in gastric cancer

Clinical relevance of the multidrug resistance‑associated protein�1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

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