MiR-7-5p suppresses stemness and enhances temozolomide sensitivity of drug-resistant glioblastoma cells by targeting Yin Yang 1

Jia, Bo; Liu, Wei; Gu, Jintao; Wang, Jiancai; Lv, Weifeng; Zhang, Wangqian; Hao, Qiang; Pang, Zhijun; Ma, Nan; Zhang, Wei; Guo, Qingdong

doi:10.1016/j.yexcr.2018.12.016

Cited by 75 publications

(53 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gao et al also found that miR-141 acted as a potential diagnostic and prognostic biomarker for OC [23], which was concurred with our results. Another study also claimed that miR-7-5p under-expression was associated with recurrence in glioblastoma patients, and that its overexpression decreased glioblastoma cell stemness [24]. Furthermore, it was also elucidated that ectopic expression of miR-7 functioned as an anti-oncogene in OC by repressing cell invasion and proliferation [10].…”

Section: Discussionmentioning

confidence: 98%

Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer

Zhang

2020

Preprint

View full text Add to dashboard Cite

Background: The molecular mechanisms of ovarian cancer (OC) remain unclear. We sought to comprehensively identify microRNAs (miRNAs) that are aberrantly expressed in metastatic OC. Methods: Differentially expressed miRNAs were screened from six pairs of primary and metastatic OC tissues; their possible functions were analyzed and target genes were predicted by bioinformatics. Then gene expression profiling results were established by reverse transcription quantitative polymerase chain reaction and western blot. Targeting relationship between miR-7-5p and TGFβ2 was validated by dual-luciferase reporter assay. CCK-8, Transwell assay, scratch test and flow cytometry were used for cell function detection after miR-7-5p overexpression. Results: Twelve miRNAs and 10 target mRNAs were differentially expressed in primary and metastatic OC tissues. ITGB3, TGFβ2 and TNC correlated to miRNA function in metastatic OC. Among all 7 miRNAs, expression of hsa-miR-141-3p, hsa-miR-7-5p, hsa-miR-187-5p, hsa-miR-200a-3p, and hsa-miR-200b-3p in metastatic OC tissues was obviously lower than that in primary OC tissues ( p < 0.05). Moreover, there was a significant correlation between hsa-miR-7-5p and TGFβ2 in OC tissues. Dual-luciferase reporter assay confirmed that hsa-miR-7-5p negatively targeted TGFβ2. After miR-7-5p overexpression, the OC cell viability and invasion were reduced, the cell cycle was blocked ( p < 0.05). Conclusions: Hsa-miR-141-3p, hsa-miR-187-5p, hsa-miR-7-5p, hsa-miR-200a-3p, and hsa-miR-200b-3p expression was prominently lower in metastatic OC than in primary OC, while TGFβ2 expression was markedly increased in metastatic OC tissues. Hsa-miR-7-5p bound to TGFβ2 3’-UTR to inhibit its expression. Hsa-miR-7-5p targeted TGFβ2 to inhibit cell proliferation, invasion and cell cycle entry.

show abstract

Section: Discussionmentioning

confidence: 98%

Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer

Zhang

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Of interest, underexpressed miR-7-5p has been documented in metastatic breast cancer [25] and invasive pancreatic cancer [26]. Another study also claimed that miR-7-5p de ciency was associated with recurrence in glioblastoma patients, and that its overexpression decreased glioblastoma cell stemness [27]. Furthermore, it was also elucidated that ectopic expression of miR-7 functioned as an anti-oncogene in OC by repressing cell invasion and proliferation [11].…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Sequencing Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer with Experimental Validations

Zhang

2020

Preprint

View full text Add to dashboard Cite

Background: Ovarian cancer (OC) is a common gynecological cancer and characterized by high metastatic potential. MicroRNAs (miRNAs, miRs) have the promise to be harnessed as prognostic and therapeutic biomarkers for OC. Herein, we sought to identify differentially expressed miRNAs and mRNAs in metastatic OC, and to validate them with functional experiments.Methods: Differentially expressed miRNAs and miRNAs were screened from six pairs of primary OC tissues and metastatic tissues using an miRStar™ Human Cancer Focus miRNA & Target mRNA PCR Array. Then, gene expression profiling results were verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The binding affinity between miR-7-5p and TGFβ2 was validated by dual-luciferase reporter assay. Expression of miR-7-5p and TGFβ2 was manipulated to assess their roles in malignant phenotypes of highly metastatic HO-8910PM cells.Results: MiRNA profiling and sequencing identified 12 miRNAs and 10 mRNAs that were differentially expressed in metastatic tissues. Gene ontology and Pathway analyses determined that 3 differentially expressed mRNAs (ITGB3, TGFβ2 and TNC) were related to OC metastasis. The results of RT-qPCR confirmed that the decrease of miR-7-5p was most significant in OC metastasis, while TGFβ2 was up-regulated in OC metastasis. Moreover, miR-7-5p targeted and negatively regulated TGFβ2. MiR-7-5p overexpression accelerated HO-8910PM cell viability and invasion, and TGFβ2 overexpression reversed the results. Meanwhile, simultaneous miR-7-5p and TGFβ2 overexpression rescued the cell activities.Conclusions: This study characterizes differentially expressed miRNAs and mRNAs in metastatic OC, where miR-7-5p and its downstream target were most closely associated with metastatic OC. Overexpression of miR-7-5p targets and inhibits TGFβ2 expression, thereby inhibiting the growth and metastasis of OC.

show abstract

“…Also, miR-7-5p levels, which target YY1, are remarkably decreased in temozolomide-resistant glioblastoma cells. Therefore, miR-7-5p is considered as a stemness-and chemoresistance-suppressive miRNA [148]. Additionally, miR-186-5p, which is down-regulated in cisplatin-resistant glioblastoma cells, targets YY1, weakens the sphere formation of glioblastoma cells, and improves the efficacy of chemotherapeutic agents [149] (Figure 2 and Table 4).…”

Section: Yy1mentioning

confidence: 99%

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

View full text Add to dashboard Cite

The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

show abstract

MiR-7-5p suppresses stemness and enhances temozolomide sensitivity of drug-resistant glioblastoma cells by targeting Yin Yang 1

Cited by 75 publications

References 38 publications

Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer

Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer

High-Throughput Sequencing Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer with Experimental Validations

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Contact Info

Product

Resources

About