MicroRNA-410-3p attenuates gemcitabine resistance in pancreatic ductal adenocarcinoma by inhibiting HMGB1-mediated autophagy

Xiong, Junjie; Wang, Dan; Wei, Ailin; Ke, Nengwen; Wang, Yichao; Tang, Jie; He, Sirong; Hu, Weiming; Liu, Xuedong

doi:10.18632/oncotarget.22494

Cited by 58 publications

(33 citation statements)

References 49 publications

(58 reference statements)

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“…Since both miR-129-3p and miR-129-5p (see Table 1) are derived from the same precursor, and both mature miRNA strands are functionally different in cells, it is feasible that over-expression of the miR-129 precursor in cancer cells using vector systems triggers cytoprotective autophagy, but inhibits ABCB1 levels. miR-410-3p HMGB1 Pancreatic cancer Over-expression of miR-410-3p improves gemcitabine-induced cell death and growth inhibition in drug-resistant cells [102] miR-520-3p ATG7 Hepatocellular carcinoma Replacement of miR-520-3p increases the sensitivity of drug-resistant cells to doxorubicin by enhancing cell death and growth inhibition [103] miR-874-3p ATG16L1 Gastric cancer Restoration of miR-874-3p sensitizes cells to 5-fluorouracil and cisplatin [104] Another recent study showed that RAB12 member RAS oncogene family (RAB12) is an endogenous mTORC1 inhibitory factor and protects cancer cells from drug-induced cell death by activating cytoprotective autophagy. RAB12 is targeted by miR-148-3p; therefore, the introduction of miR-148-3p in cancer cells can reverse therapeutic resistance [89] (Table 3).…”

Section: Mirnas Regulating Mtor and Mtorc1mentioning

confidence: 99%

“…A reduced form of HMGB1 in the extracellular space also facilitates BECLIN1-dependent autophagy [106]. Direct inhibition of HMGB1 by miR-34-5p and miR-410-3p impedes autophagy induction, reversing resistance to several chemotherapeutic agents [92,102]. Likewise, HMGB2 is presumed to promote autophagy by the same mechanisms as HMGB1.…”

Section: Mirnas Regulating Hmgbsmentioning

confidence: 99%

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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: Mirnas Regulating Mtor and Mtorc1mentioning

confidence: 99%

Section: Mirnas Regulating Hmgbsmentioning

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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“…[14][15][16] Recent studies have identified miR-410-3p, a novel cancer-related miRNA, as a tumor suppressor in human breast cancer and pancreatic ductal adenocarcinoma. 17,18 Nonetheless, the biological role of miR-410-3p in glioma is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

<p>Decreased expression of miR-410-3p correlates with poor prognosis and tumorigenesis in human glioma</p>

Wang

Huang

Rao

et al. 2019

CMAR

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Background: Gliomas are the most common type of primary tumors in the central nervous system. This study aimed to investigate the biological role of miR-410-3p in glioma and elucidate the potential molecular mechanisms involved. Methods: The expression levels of miR-410-3p in clinical tissue samples and glioma cell lines were determined using qRT-PCR analysis. The clinical significance of miR-410-3p in glioma was evaluated using Kaplan-Meier survival analysis and Fisher's exact test. The effects of miR-410-3p on glioma cell proliferation, apoptosis, migration and invasion were investigated using MTT assays, flow cytometry, transwell migration and invasion assays. Besides, corresponding mechanistic studies were carried out. Results: miR-410-3p was significantly down-regulated in glioma tissues. Besides, Kaplan-Meier analysis demonstrated that patients with low miR-410-3p expression had a shorter overall survival. Decreased miR-410-3p expression was associated with larger tumor size, lower Karnofsky performance score (KPS), and higher World Health Organization (WHO) grade. Over-expression of miR-410-3p suppressed cell proliferation, migration, and invasion, and accelerated apoptosis; whereas depletion of miR-410-3p facilitated cell proliferation, migration, and invasion, and inhibited apoptosis. Mechanistic investigations demonstrated that Ras-related protein 1A (RAP1A) was a direct target of miR-410-3p, and that rescue of RAP1A expression reversed miR-410-3p over-expression-induced inhibitory effects on cell proliferation, migration, and invasion. Notably, miR-410-3p over-expression repressed tumor growth in mouse xenograft models. Conclusion: Our findings indicate that miR-410-3p functions as a tumor suppressor in glioma by directly targeting RAP1A. Thus, this study may provide some new insights into gliomagenesis and progression.

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“…They are vital gene expression regulators and can completely or incompletely interact with the 3'-untranslated regions (3'-UTRs) of their target messenger RNAs (mRNAs) to prevent mRNA translation and/or promote mRNA degradation (7). Recently, several miRNAs have been identified to be differently expressed in PDAC, including miRNA (miR)-7-5p (8), miR-410-3p (9), miR-212 (10) and miR-454 (11). The aberrant expression of miRNAs is closely associated with the development and malignant progression of PDAC and serve as oncogenes or tumour suppressors (12,13).…”

Section: Introductionmentioning

confidence: 99%

“…The aberrant expression of miRNAs is closely associated with the development and malignant progression of PDAC and serve as oncogenes or tumour suppressors (12,13). miRNAs regulate the multiple biological behaviours of PDAC cells, including cell proliferation, apoptosis, cell cycle, lymphangiogenesis, invasion, metastasis, epithelial-mesenchymal transition and chemotherapeutic resistance (9,11,(14)(15)(16). Therefore, miRNAs are potential diagnostic biomarkers and therapeutic targets for patients with PDAC, and the association between miRNAs and PDAC requires further clarification.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑766 inhibits the malignant biological behaviours of pancreatic ductal adenocarcinoma by directly targeting ETS1

Yan

Yue

et al. 2018

Mol Med Report

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Increasing evidence indicates that numerous microRNAs (miRNAs) are altered in pancreatic ductal adenocarcinoma (PDAC), and their alterations significantly influence the malignant behaviour of PDAC. Therefore, identifying miRNAs associated with PDAC and their biological roles in the disease may provide promising therapeutic opportunities. Alteration of the expression of miRNA-766 (miR-766) has been previously reported in several types of human malignancy. However, to the best of our knowledge, whether miR-766 exhibits different expression patterns in PDAC and its underlying functions in the progression of PDAC remain to be elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect miR-766 expression levels in PDAC tissues and cell lines. The effects of miR-766 upregulation on PDAC cell proliferation and invasion were evaluated using MTT and invasion assays, respectively. The mechanisms underlying the role of miR-766 in PDAC cells were explored using bioinformatics analysis, luciferase reporter assay, RT-qPCR and western blot analysis. It was found that miR-766 was significantly downregulated in PDAC tissues and cell lines. The detailed roles of miR-766 in the progression of PDAC were characterised using Panc-1 and Aspc-1 cell lines. The results revealed that the upregulation of miR-766 restricted the proliferation and invasion of PDAC cells. Through a series of experiments, it was found that E26 transformation specific-1 (ETS1) was a direct target of miR-766 in PDAC cells. Furthermore, ETS1 knockdown simulated the inhibitory effects of the overexpression of miR-766 on PDAC cells, whereas the effects of miR-766 restoration on the PDAC cells were reversed by overexpressing ETS1. In conclusion, the findings of the present study demonstrate that miR-766 offers potential as a therapeutic target for patients with PDAC.

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MicroRNA-410-3p attenuates gemcitabine resistance in pancreatic ductal adenocarcinoma by inhibiting HMGB1-mediated autophagy

Cited by 58 publications

References 49 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

<p>Decreased expression of miR-410-3p correlates with poor prognosis and tumorigenesis in human glioma</p>

MicroRNA‑766 inhibits the malignant biological behaviours of pancreatic ductal adenocarcinoma by directly targeting ETS1

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