MiR-7-5p-mediated downregulation of PARP1 impacts DNA homologous recombination repair and resistance to doxorubicin in small cell lung cancer

Lai, Jinzhi; Yang, Hainan; Zhu, Yanyang; Ruan, Mei; Huang, Yayu; Zhang, Qiuyu

doi:10.1186/s12885-019-5798-7

Cited by 77 publications

(60 citation statements)

References 35 publications

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“…PARP1 is down-regulated by miR-7-5p, leading to impaired DNA damage repair. Notably, miR-7-5p levels show a negative correlation with the status of doxorubicin resistance [55] (Table 2). Cells 2020, 9, 29 7 of 32…”

Section: Mir-7-5pmentioning

confidence: 99%

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

Seo

Moeng

Sim³

et al. 2019

Cells

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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...

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Section: Mir-7-5pmentioning

confidence: 99%

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

Seo

Moeng

Sim³

et al. 2019

Cells

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“…However, these results although positive, cannot be exclusively linked to the antioxidant effect of HT, as they are achieved at concentrations (≥75 µM) clearly over the antioxidant ones (≥5 µM) 23 . PARP-1 is also regulated by a number of microRNAs 49,50 , and HT is known to modulate the expression of these small non-coding RNA molecules 51 . Thus, this mechanism could be a plausible additional contributor to PARP-1 down-regulation.…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between hydroxytyrosol, a major olive oil phenol, and HIF-1 in MCF-7 breast cancer cells

Calahorra

Martı́nez-Lara

Granadino‐Roldán

et al. 2020

Sci Rep

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Olive oil intake has been linked with a lower incidence of breast cancer. Hypoxic microenvironment in solid tumors, such as breast cancer, is known to play a crucial role in cancer progression and in the failure of anticancer treatments. HIF-1 is the foremost effector in hypoxic response, and given that hydroxytyrosol (HT) is one of the main bioactive compounds in olive oil, in this study we deepen into its modulatory role on HIF-1. Our results in MCF-7 breast cancer cells demonstrate that HT decreases HIF-1α protein, probably by downregulating oxidative stress and by inhibiting the PI3K/ Akt/mTOR pathway. Strikingly, the expression of HIF-1 target genes does not show a parallel decrease. Particularly, adrenomedullin and vascular endothelial growth factor are up-regulated by high concentrations of HT even in HIF-1α silenced cells, pointing to HIF-1-independent mechanisms of regulation. In fact, we show, by in silico modelling and transcriptional analysis, that high doses of HT may act as an agonist of the aryl hydrocarbon receptor favoring the induction of these angiogenic genes. In conclusion, we suggest that the effect of HT in a hypoxic environment is largely affected by its concentration and involves both HIF-1 dependent and independent mechanisms.

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“…The interregulation of CCAT1 and miRNAs including miR7 has been studies in different cancers including NPC (Wang, Zhang & Hao, 2017;Zhang et al, 2017a;Zhang, Cai, Jiang & Xu, 2019); CCAT1 increased cancer cell proliferation and metastasis by acting as a competing endogenous RNA to sponging miRNAs resulting in regulation of gene expression or through regulation of other signaling regulatory axis (Xu et al, 2018;Zhang, Cai, Jiang & Xu, 2019). Bioinformatics analysis and luciferase reporter experiments showed that several lncRNAs were direct target of miR7-5p that were involved in the tumor growth, migration, invasion, and chemoresistance in several cancer types (Dong, Xie & Xu, 2019;Jia et al, 2019;Lai, Yang, Zhu, Ruan, Huang & Zhang, 2019;Mo, Liu, Li & Cui, 2019). One study showed that silencing of CCAT1 significantly inhibited the migration, invasion, and reversed EMT phenotype of intrahepatic cholangiocarcinoma cells through directly binding to miR-152 (Zhang et al, 2017b).…”

Section: Discussionmentioning

confidence: 99%

“…Bioinformatic analysis indicated that poly ADP-ribose polymerase 1 (PARP1) was a direct target of miR7-5p, and PARP1 expression was inhibited by miR7-5p in small cell lung cancer cells. This resulted in sensitizing cancer cells to doxorubicin suggesting that the regulation of miR7-5p could be potential for overcoming chemoresistance in lung cancer (Lai, Yang, Zhu, Ruan, Huang & Zhang, 2019). Regardless, the potential mechanism underlying the regulation of miR7-5p involved in the tumorigenesis and progression of NPC remains unknown.…”

Section: Introductionmentioning

confidence: 99%

The regulation and interaction of colon cancer‐associated transcript‐1 and miR7‐5p contribute to the inhibition of SP1 expression by solamargine in human nasopharyngeal carcinoma cells

Tang

et al. 2019

Phytotherapy Research

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Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy with higher incidence in Southern China and Southeast Asia. Solamargine (SM), a steroidal alkaloid glycoside, has been shown to have anticancer properties. However, the underlying mechanism involved remains undetermined. In this study, we showed that SM inhibited the growth of NPC cells. Mechanistically, we found that solamargine decreased lncRNA colon cancer-associated transcript-1 (CCAT1) and increased miR7-5p expression. There was a reciprocal interaction of CCAT1 and miR7-5p. In addition, SM inhibited the expression of SP1 protein and promoter activity, which was strengthened by miR7-5p mimics and inhibited by overexpressed CCAT1.MiR7-5p could bind to 3'-UTR of SP1 and attenuated SP1 gene expression. Exogenously expressed SP1 feedback resisted SM-increased miR7-5p expression and more importantly reversed SM-inhibited growth of NPC cells. Finally, SM inhibited NPC tumor growth in vivo. Collectively, our results show that SM inhibits the growth of NPC cells through reciprocal regulation of CCAT1 and miR7-5p, followed by inhibition of SP1 gene expression in vitro and in vivo. The interregulation and correlation among CCAT1, miR7-5p and SP1, and the feedback regulatory loop unveil the novel molecular mechanism underlying the overall responses of SM in anti-NPC.

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MiR-7-5p-mediated downregulation of PARP1 impacts DNA homologous recombination repair and resistance to doxorubicin in small cell lung cancer

Cited by 77 publications

References 35 publications

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

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

Crosstalk between hydroxytyrosol, a major olive oil phenol, and HIF-1 in MCF-7 breast cancer cells

The regulation and interaction of colon cancer‐associated transcript‐1 and miR7‐5p contribute to the inhibition of SP1 expression by solamargine in human nasopharyngeal carcinoma cells

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