MSC-induced lncRNA HCP5 drove fatty acid oxidation through miR-3619-5p/AMPK/PGC1α/CEBPB axis to promote stemness and chemo-resistance of gastric cancer

Wu, Honglei; Liu, Bin; Chen, Zhaosheng; Li, Guangchun; Zhang, Zhen

doi:10.1038/s41419-020-2426-z

Cited by 175 publications

(137 citation statements)

References 61 publications

(100 reference statements)

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“…Therefore, the call for investigation in the mechanisms underlying the onset and progression of GC is pressing. 4 Endogenous RNAs as they are, microRNAs (miRNAs) can reversely regulate approximately 30% of human genes through binding to the complementary 3 'untranslated region (3ʹ-UTR). 5 According to reports, the role of miRNAs varies in different cancers.…”

Section: Introductionmentioning

confidence: 99%

<p>Effects of miR-384 and miR-134-5p Acting on YY1 Signaling Transduction on Biological Function of Gastric Cancer Cells</p>

Zhong

Wang

et al. 2020

OTT

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Objective: To explore the related influencing mechanism of miR-384 and miR-134-5p acting on Yin Yang 1 (YY1) signaling transduction on the biological function of gastric cancer (GC) cells. Methods: miR-384, miR-134-5p and YY1 levels in human GC cell lines KATO III, MKN-45, SNU-1 and normal gastric cell line GES-1 were measured by polymerase chain reaction (PCR). Dual luciferase reporter (DLR) gene assay and Western blot (WB) were employed for correlation analysis between miR-384, miR-134-5p and YY1. miR-384-inhibitor, miR-384mimics, empty plasmid (miRNA-NC) and sh-YY1 were transfected into KATO III cells. Cell proliferation was determined by 3-(4,5-Dimethylthiazolyl-2)-2,5-Diphenyl Tetrazolium Bromide (MTT), cell invasion was measured by Transwell, and apoptosis was analyzed by flow cytometry (FC). Results: In KATO III, MKN-45 and SNU-1 cell lines, YY1 was upregulated while miR-384 and miR-134-5p were downregulated (P<0.001). The expression of miR-134-5p in the miR-134-5p-inhibitor group was significantly lower (P<0.001), while that in the miR-134-5pmimics group was significantly higher (P<0.001). The expression of miR-384 in the miR-384-inhibitor group was significantly lower (P<0.001), and that in the miR-384-mimics group was significantly higher as compared to the NC group (P<0.001). Both miR-384 and miR-134-5p overexpression could inhibit cell proliferation and invasion, and promote apoptosis. As detected by WB, overexpressed miR-384 and miR-134-5p inhibited the expression of EMT-related molecular markers. Compared with sh-YY1, the number of cells in S phase decreased, the pro-apoptotic proteins boosted statistically, and the anti-apoptotic proteins declined notably after transfecting miR-134-5p-mimics/sh-YY1 or miR-384-mimics/sh-YY1 (P<0.05). The tumor growth rate of nude mice in miR-134-5p/sh-YY1 and miR-384/sh-YY1 groups were significantly lower than those in sh-YY1 group (all P<0.001). Conclusion: By targeting YY1 signaling transduction, miR-134-5p and miR-384 can alter the growth and apoptosis of GC cells, which are promising targets for new therapeutics of GC.

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Section: Introductionmentioning

confidence: 99%

<p>Effects of miR-384 and miR-134-5p Acting on YY1 Signaling Transduction on Biological Function of Gastric Cancer Cells</p>

Zhong

Wang

et al. 2020

OTT

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“…An increasing number of studies have demonstrated the critical modulating role of lncRNAs in tumor stemness phenotype as well as chemosensitivity (26,27). In the current study, we for the rst time systematically explored the potential signi cance of LINC00680 in HCC stemness properties and sensitivity to conventional HCC chemotherapeutic drugs, such as 5-Fu.…”

Section: Discussionmentioning

confidence: 99%

LINC00680 Enhances Hepatocellular Carcinoma Stemness Behavior and Chemoresistance by Sponging miR-568 to Upregulate AKT3

Shu

Wang

et al. 2020

Preprint

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Background: Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity. Methods: QRT-PCR was used to detect the expression of LINC00680, miR-568 and AKT3 in tissue specimen and cell lines. Gain- or loss-of function assays were applied to access the function of LINC00680 in HCC cells, including cell proliferation and stemness properties. HCC stemness and chemosensitivity were determined by sphere formation, cell viability and colony formation. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull down assays were performed to examine the interaction between LINC00680 and miR-568 as well as that between miR-568 and AKT3. A nude mouse xenograft model was established for the in vivo study.Results: We found that LINC00680 was remarkably upregulated both in HCC tissue and cell lines. Patients with high level of LINC00680 had poorer prognosis. LINC00680 overexpression significantly enhanced HCC cell stemness and decreased in vitro and in vivo chemosensitivity to 5-fluorouracil (5-Fu), whereas LINC00680 knockdown led to opposite results. Mechanism study revealed that LINC00680 regulated HCC stemness and chemosensitivity through sponging miR-568, thereby expediting the expression of AKT3, which further activated its downstream signaling molecules, including mTOR, elF4EBP1, and p70S6K.Conclusion: LINC00680 promotes HCC stemness properties and decreases chemosensitivity through sponging miR-568 to activate AKT3, suggesting that LINC00680 might be a potentially important HCC diagnosis marker and therapeutic target.

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“…At present, a large number of studies have shown that, in addition to mRNAs, non-coding RNAs also related to drug resistance of cancers, including gastric cancer [33], bladder cancer [34], lung adenocarcinoma [35]. Moreover, in CRC drug resistance studies, it was reported that LINC00957 could increase 5uorouracil resistance and result in poor survival of patients [36], hsa_circ_0079662 was related to oxaliplatin resistance via TNF-α pathway [25], microRNA-375-3p was involved in 5-uorouracil resistance by targeting thymidylate synthase [37].…”

Section: Discussionmentioning

confidence: 99%

Analysis of mRNAs and ncRNAs and Prediction Competing Endogenous RNA Networks in Colorectal Cancer Chemo-Resistance by Whole-Transcriptome Sequencing

Yao

Zhou

Huang

et al. 2020

Preprint

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Abstract Background: Chemo-resistance is a major clinical obstacle to the treatment of colorectal cancer (CRC), mRNAs and non-coding RNAs (ncRNAs) have been reported to modulate the development of chemo-resistance. However, the profiles of mRNAs and ncRNAs as well as competing endogenous RNA (ceRNA) networks in CRC chemo-resistance are still unclear, and whether different drug resistance of CRC have the same mechanisms also needs to be explored. This study aims to uncover the expression of mRNAs and ncRNAs in parental cell lines and different chemo-resistant cell lines, and construct ceRNA regulatory networks by whole-transcriptome sequencing.Methods: The expression of mRNAs and ncRNAs in parental cell lines and drug-resistant cell lines were identified by whole-transcriptome sequencing and bioinformatics methods.Results: A total of 1779 mRNAs, 64 miRNAs, 11 circRNAs and 295 lncRNAs were common differentially expressed in two different chemo-resistant cell lines when compared with the control. In addition, 5,767 lncRNA-miRNA-mRNA relationship pairs and 47 circRNA-miRNA-mRNA pathways were constructed according to ceRNA regulatory rules, in which AC109322.2-hsa-miR-371a-5p-BTNL3 and hsacirc_027876-hsa-miR-582-3p-FREM1 were identified as the most potential ceRNA networks involved in drug resistance to CRC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of two ceRNA regulatory networks showed that the TNF signaling pathway may be crucial in the process of CRC drug resistance.Conclusions: A large number of mRNAs and ncRNAs in chemo-resistant cell lines were different expressed, which may play pivotal roles in development of drug resistance through the ceRNA regulatory network. This study may improve our understanding of the underlying mechanisms and provide a promising therapeutic strategy for CRC chemo-resistance.

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MSC-induced lncRNA HCP5 drove fatty acid oxidation through miR-3619-5p/AMPK/PGC1α/CEBPB axis to promote stemness and chemo-resistance of gastric cancer

Cited by 175 publications

References 61 publications

<p>Effects of miR-384 and miR-134-5p Acting on YY1 Signaling Transduction on Biological Function of Gastric Cancer Cells</p>

<p>Effects of miR-384 and miR-134-5p Acting on YY1 Signaling Transduction on Biological Function of Gastric Cancer Cells</p>

LINC00680 Enhances Hepatocellular Carcinoma Stemness Behavior and Chemoresistance by Sponging miR-568 to Upregulate AKT3

Analysis of mRNAs and ncRNAs and Prediction Competing Endogenous RNA Networks in Colorectal Cancer Chemo-Resistance by Whole-Transcriptome Sequencing

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