miR-374 mediates the malignant transformation of gastric cancer-associated mesenchymal stem cells in an experimental rat model

Ji, Runbi; Zhang, Xu; Qian, Hui; Gu, Hongchen; Sun, Zixun; Mao, Fei; Yan, Yongmin; Chen, Jingyan; Liang, Zhaofeng; Xu, Wenrong

doi:10.3892/or.2017.5831

Cited by 19 publications

(16 citation statements)

References 26 publications

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“…The diagnostic value of serum miR-374a-5p was higher than traditional diagnostic markers, such as alpha fetoprotein (AFP) or carcino-embryonic antigen (CEA) 16 . In addition, we found that the expression of miR-374a-5p was increased in the serum of patients with pre-cancerous gastric lesions, which was consistent with our previous study showing that the expression of miR-374a-5p was also increased in the serum of MNNG-exposed rats with atypical hyperplasia in gastric tissues 4 . Thus, miR-374a-5p may serve as a potential biomarker for the early diagnosis of gastric cancer.…”

Section: Discussionsupporting

confidence: 91%

“…Our recent study revealed that miR-374 promoted the proliferation and migration of transformed mesenchymal stem cells (MSCs) by regulating the Wnt5a/β-catenin signaling pathway, which, to a certain extent, contributed to the transformation of rat bone marrow-derived MSCs to the K3 tumor cell line 3 . In addition, the upregulation of miR-374 in MSCs from the gastritis tissues of MNNG (N-methyl-N′-nitro-N-nitrosoguanidine)-exposed rats could increase their proliferation and migration abilities 4 . Other studies showed that miR-374-5p overexpression promoted the proliferation, migration, and invasion of gastric cancer cells by targeting SRCIN1 and RECK genes 5, 6.…”

Section: Introductionmentioning

confidence: 98%

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miR-374a-5p: A New Target for Diagnosis and Drug Resistance Therapy in Gastric Cancer

et al. 2019

Molecular Therapy - Nucleic Acids

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Chemoresistance is one of the causes associated with poor prognosis in gastric cancer. MicroRNAs (miRNAs) are important regulators of chemoresistance. Exosome-mediated delivery of anti-cancer molecules and drugs have emerged as a new approach for cancer therapy. We first examined the expression of miR-374a-5p in gastric cancer serum by qRT-PCR and explored the clinicopathological parameters. We then performed in vitro cell and molecular studies, including CCK-8 assay, flow cytometry, qRT-PCR, and western blot, to determine the roles of miR-374a-5p in gastric cancer chemoresistance and identified its downstream target by luciferase reporter assay. We also used in vivo animal studies to evaluate the therapeutic efficacy of miR-374a-5p inhibitor and exosome-mediated delivery of miR-374a-5p inhibitor in gastric cancer. miR-374a-5p expression level was elevated in gastric cancer serum, and its upregulation predicted poor prognosis. miR-374a-5p overexpression promoted while miR-374a-5p knockdown inhibited gastric cancer chemoresistance in vitro and in vivo. miR-374a-5p bound to Neurod1 to antagonize its effect on chemoresistance. Exosome-mediated delivery of miR-374a-5p inhibitor could increase Neurod1 expression, promote cell apoptosis, and suppress chemoresistance. miR-374a-5p had a promoting role in gastric cancer chemoresistance, which would provide a novel biomarker for gastric cancer diagnosis and prognosis and offer a potential target for gastric cancer drug resistance therapy.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 98%

miR-374a-5p: A New Target for Diagnosis and Drug Resistance Therapy in Gastric Cancer

et al. 2019

Molecular Therapy - Nucleic Acids

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“…Xie J showed that the expression of miR‐374b‐5p was up‐regulated and conducive to gastric cancer cell invasion and metastasis via inhibiting the expression of RECK . Ji et al presented that the up‐regulation of miR‐374 mediated the malignant transformation of gastric cancer‐associated mesenchymal stem cells and represented a novel avenue for gastric cancer therapy with an experimental rat model. In the same year, Sierzega et al found that miR‐374 was abnormally expressed in the primary tissue of gastric cancer, but its expression was not changed in the serum of GC patients …”

Section: The Role Of Mir‐374 In Tumorigenesismentioning

confidence: 99%

The latest progress on miR‐374 and its functional implications in physiological and pathological processes

Bian

Zhou

et al. 2019

J Cellular Molecular Medi

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Non‐coding RNAs (ncRNAs) have been emerging players in cell development, differentiation, proliferation and apoptosis. Based on their differences in length and structure, they are subdivided into several categories including long non‐coding RNAs (lncRNAs >200nt), stable non‐coding RNAs (60‐300nt), microRNAs (miRs or miRNAs, 18‐24nt), circular RNAs, piwi‐interacting RNAs (26‐31nt) and small interfering RNAs (about 21nt). Therein, miRNAs not only directly regulate gene expression through pairing of nucleotide bases between the miRNA sequence and a specific mRNA that leads to the translational repression or degradation of the target mRNA, but also indirectly affect the function of downstream genes through interactions with lncRNAs and circRNAs. The latest studies have highlighted their importance in physiological and pathological processes. MiR‐374 family member are located at the X‐chromosome inactivation center. In recent years, numerous researches have uncovered that miR‐374 family members play an indispensable regulatory role, such as in reproductive disorders, cell growth and differentiation, calcium handling in the kidney, various cancers and epilepsy. In this review, we mainly focus on the role of miR‐374 family members in multiple physiological and pathological processes. More specifically, we also summarize their promising potential as novel prognostic biomarkers and therapeutic targets from bench to bedside.

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“…It has been reported that MSCs can be recruited to tumors and participate in the formation of the tumor stroma [ 43 – 47 ]. Recent studies have shown that MSCs can undergo malignant transformation when they are cultured for a long period of time or in a tumor-like environment, although the underlying mechanism remains unknown [ 10 , 30 , 48 , 49 ]. In this study, we induced MSCs to undergo malignant transformation by indirectly coculturing them with C6 glioma cells.…”

Section: Discussionmentioning

confidence: 99%

MRI detection of the malignant transformation of stem cells through reporter gene expression driven by a tumor-specific promoter

et al. 2021

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Background Existing evidence has shown that mesenchymal stem cells (MSCs) can undergo malignant transformation, which is a serious limitation of MSC-based therapies. Therefore, it is necessary to monitor malignant transformation of MSCs via a noninvasive imaging method. Although reporter gene-based magnetic resonance imaging (MRI) has been successfully applied to longitudinally monitor MSCs, this technique cannot distinguish the cells before and after malignant transformation. Herein, we investigated the feasibility of using a tumor-specific promoter to drive reporter gene expression for MRI detection of the malignant transformation of MSCs. Methods The reporter gene ferritin heavy chain (FTH1) was modified by adding a promoter from the tumor-specific gene progression elevated gene-3 (PEG3) and transduced into MSCs to obtain MSCs-PEG3-FTH1. Cells were induced to undergo malignant transformation via indirect coculture with C6 glioma cells, and these transformed cells were named MTMSCs-PEG3-FTH1. Western blot analysis of FTH1 expression, Prussian blue staining and transmission electron microscopy (TEM) to detect intracellular iron, and MRI to detect signal changes were performed before and after malignant transformation. Then, the cells before and after malignant transformation were inoculated subcutaneously into nude mice, and MRI was performed to observe the signal changes in the xenografts. Results After induction of malignant transformation, MTMSCs demonstrated tumor-like features in morphology, proliferation, migration, and invasion. FTH1 expression was significantly increased in MTMSCs-PEG3-FTH1 compared with MSCs-PEG3-FTH1. Prussian blue staining and TEM showed a large amount of iron particles in MTMSCs-PEG3-FTH1 but a minimal amount in MSCs-PEG3-FTH1. MRI demonstrated that the T2 value was significantly decreased in MTMSCs-PEG3-FTH1 compared with MSCs-PEG3-FTH1. In vivo, mass formation was observed in the MTMSCs-PEG3-FTH1 group but not the MSCs-PEG3-FTH1 group. T2-weighted MRI showed a significant signal decrease, which was correlated with iron accumulation in the tissue mass. Conclusions We developed a novel MRI model based on FTH1 reporter gene expression driven by the tumor-specific PEG3 promoter. This approach could be applied to sensitively detect the occurrence of MSC malignant transformation.

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miR-374 mediates the malignant transformation of gastric cancer-associated mesenchymal stem cells in an experimental rat model

Cited by 19 publications

References 26 publications

miR-374a-5p: A New Target for Diagnosis and Drug Resistance Therapy in Gastric Cancer

miR-374a-5p: A New Target for Diagnosis and Drug Resistance Therapy in Gastric Cancer

The latest progress on miR‐374 and its functional implications in physiological and pathological processes

MRI detection of the malignant transformation of stem cells through reporter gene expression driven by a tumor-specific promoter

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