Identification of miR-29c and its Target FBXO31 as a Key Regulatory Mechanism in Esophageal Cancer Chemoresistance: Functional Validation and Clinical Significance

Li, Bin; Pan, Hong; Zheng, Can‐Can; Dai, Wei; Chen, Wen-You; Yang, Qiong; Liang, Han; Tsao, Sai Wah; Chan, Kin; Lee, Nikki Pui Yue; Law, Simon; Li, Xu; Li, En Min; Chan, Kwok Wah; Qin, Yan; Guan, Xin Yuan; Lung, Maria Li; He, Qing‐Yu; Xu, Wen; Cheung, Any

doi:10.7150/thno.30372

Cited by 52 publications

(36 citation statements)

References 40 publications

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“…Studies have reported that miR-338-5p and miR-200c enhance the radiosensitivity of ESCC by inducing apoptosis and cell cycle arrest in tumor cells, respectively [36,126]. Similarly, miR-29c, miR-125a-5p, and miR-1 enhance ESCC cell sensitivity for anticancer drugs such as 5-fluorouracil, cisplatin, and gefitinib, respectively [123][124][125]. As shown in Table 1, these reported miRNAs target different molecules or signaling pathways to decrease chemoresistance and radioresistance in ESCC.…”

Section: Non-coding Rnas Influence Chemoresistance and Radioresistancmentioning

confidence: 99%

Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma

Feng

Zhang

Yao

et al. 2019

IJMS

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Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.

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Section: Non-coding Rnas Influence Chemoresistance and Radioresistancmentioning

confidence: 99%

Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma

Feng

Zhang

Yao

et al. 2019

IJMS

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“…Despite 5‐FU being an antimetabolic agent widely used in treating gastrointestinal cancers, the response rate of esophageal carcinoma to 5‐FU is only 15% . Emerging evidence indicates that miRNAs are associated with chemoresistance, but relatively few miRNAs were experimentally validated to have the ability to regulate the sensitivity of ESCC cells to 5‐FU treatment . Our present study found that miR‐338‐5p was underexpressed in 5‐FU‐resistant ESCC cells, and that ectopic overexpression of miR‐338‐5p in these cells could increase their sensitivity to 5‐FU treatment both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 47%

“…We found that ectopic overexpression of miR‐377, which targeted CD133 and suppressed cancer stemness, had a chemosensitizing effect on ESCC cells . More recently, we identified the miR‐29c‐3p/FBXO31‐p38 axis as a key regulator of chemoresistance in ESCC . Our previous studies also showed that Id‐1 and its downstream PI3K/Akt pathway play an essential role in promoting chemoresistance in ESCC .…”

Section: Introductionmentioning

confidence: 77%

MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1

Liang

Cui

et al. 2019

Cancer Science

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5-Fluorouracil (5-FU) is a chemotherapeutic agent commonly used to treat esophageal squamous cell carcinoma (ESCC), but acquisition of chemoresistance frequently occurs and the underlying mechanisms are not fully understood. We found that mi-croRNA (miR)-338-5p was underexpressed in ESCC cells with acquired 5-FU chemoresistance. Forced expression of miR-338-5p in these cells resulted in downregulation of Id-1, and restoration of both in vitro and in vivo sensitivity to 5-FU treatment. The effects were abolished by reexpression of Id-1. In contrast, miR-338-5p knockdown induced 5-FU resistance in chemosensitive esophageal cell lines, and knockdown of both miR-338-5p and Id-1 resensitized the cells to 5-FU. In addition, miR-338-5p had suppressive effects on migration and invasion of ESCC cells. Luciferase reporter assay confirmed a direct interaction between miR-338-5p and the 3′-UTR of Id-1. We also found that miR-338-5p was significantly downregulated in tumor tissue and serum samples of patients with ESCC. Notably, low serum miR-338-5p expression level was associated with poorer survival and poor response to 5-FU/cisplatin-based neoadjuvant chemoradiotherapy. In summary, we found that miR-338-5p can modulate 5-FU chemoresistance and inhibit invasion-related functions in ESCC by negatively regulating Id-1, and that serum miR-338-5p could be a novel noninvasive prognostic and predictive biomarker in ESCC. K E Y W O R D Schemoresistance, circulating miRNA, esophageal cancer, Id-1, miR-338-5p

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“…Several miRNAs have been discovered as biomarkers of esophageal neoplasms. For instance, miR-29c was downregulated in tumor and serum samples from esophageal neoplasm patients, which could be regarded as a promising non-invasive biomarker [81]. After implementing HRNMFMDA on esophageal neoplasms, all of the topranked 20 and 49 out of the top-ranked 50 predicted results were verified through one of the external databases or more (see Supplementary Table S2).…”

Section: Case Studiesmentioning

confidence: 99%

Identifying Potential miRNA-Disease Associations Based on an Improved Manifold Learning Framework

Tang

et al. 2020

IEEE Access

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Adequate evidence has shown that miRNA-disease interactions are strongly involved in the pathological processes of complex human diseases. However, it is commonly time-consuming and laborintensive to utilize laboratory biological experiments to reveal unknown miRNA-disease pairs. Since the previously proposed calculation model has more or fewer deficiencies, we developed the semi-supervised method called Hessian Regularized Non-negative Matrix Factorization Method for miRNA-disease Association prediction (HRNMFMDA). This model introduced Hessian regularization into the NMF framework to preserve the local manifold information and increased an l 2,1-norm penalty term to ensure the feature selection of the coding matrix and an approximate orthogonal constraint to obtain discriminative information. In the model performance evaluation, HRNMFMDA outperformed eight existing models, achieving AUC values of 0.9074, 0.8618, and 0.9044+/−0.0080 in the global leave-one-out cross-validation (LOOCV), local LOOCV and 5-fold cross-validation, respectively. In addition, we applied HRNMFMDA to several highincidence human carcinomas via three kinds of case studies. Almost all predicted miRNAs were confirmed by external databases derived from experimental literature. Therefore, the conclusion can be drawn that HRNMFMDA is reliable for revealing uncovered miRNA-disease pairs.

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Identification of miR-29c and its Target FBXO31 as a Key Regulatory Mechanism in Esophageal Cancer Chemoresistance: Functional Validation and Clinical Significance

Cited by 52 publications

References 40 publications

Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma

Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma

MicroRNA‐338‐5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id‐1

Identifying Potential miRNA-Disease Associations Based on an Improved Manifold Learning Framework

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