MicroRNA-20a-mediated loss of autophagy contributes to breast tumorigenesis by promoting genomic damage and instability

Liu, L; He, Jie; Xiang, Wei; Wan, Guohui; Lao, Yuanzhi; Xu, Wei; Li, Z; Hu, Hongyi; Hu, Zhiliang; Luo, Xu; Wu, Jiangbin; Xie, Weidong; Zhang, Y; Xu, Ning

doi:10.1038/onc.2017.193

Cited by 56 publications

(57 citation statements)

References 55 publications

(64 reference statements)

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“…Previous studies indicated that miR‐20a could impair hypoxia‐induced autophagy by targeting ATG16L1 in ischemic kidney injury or osteoclast differentiation . Moreover, Li et al found that miR‐20a and miR‐20b negatively regulated autophagy by targeting RB1CC1/FIP200 in breast cancer. A recent study reported that miR‐20a mediated loss of autophagy by targeting several key regulators of autophagy, including BECN1, ATG16L1, and SQSTM1, under the basal and nutrient starvation condition in breast cancer .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Li et al found that miR‐20a and miR‐20b negatively regulated autophagy by targeting RB1CC1/FIP200 in breast cancer. A recent study reported that miR‐20a mediated loss of autophagy by targeting several key regulators of autophagy, including BECN1, ATG16L1, and SQSTM1, under the basal and nutrient starvation condition in breast cancer . Because of the multiple potential targets of miR‐20a, we examine a series of autophagy‐related protein, as well as AKT/mTOR, in LoVo and SW48 cells.…”

Section: Discussionmentioning

confidence: 99%

“…(mean ± SD of independent experiments, n = 3, *P < 0.05, **P < 0.01). CoCl 2 , cobalt chloride; GFP, green fluorescent protein; NC, negative control; RFP, red fluorescent protein; ROI, region of interest [Color figure can be viewed at wileyonlinelibrary.com]regulators of autophagy, including BECN1, ATG16L1, and SQSTM1, under the basal and nutrient starvation condition in breast cancer 51.…”

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confidence: 99%

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miR‐20a inhibits hypoxia‐induced autophagy by targeting ATG5/FIP200 in colorectal cancer

Che

Wang

Huang

et al. 2019

Molecular Carcinogenesis

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Autophagy is a highly conserved lysosome‐mediated protective cellular process in which cytosolic components, including damaged organelles and long‐lived proteins, are cleared. Many studies have shown that autophagy was upregulated in hypoxic regions. However, the precise molecular mechanism of hypoxia‐induced autophagy in colorectal cancer (CRC) is still elusive. In this study, we found that miR‐20a was significantly downregulated under hypoxia in colon cancer cells, and overexpression of miR‐20a alleviated hypoxia‐induced autophagy. Moreover, miR‐20a inhibits the hypoxia‐induced autophagic flux by targeting multiple key regulators of autophagy, including ATG5 and FIP200. Furthermore, by dual‐luciferase assay we demonstrated that miR‐20a directly targeted the 3′‐untranslated region of ATG5 and FIP200, regulating their messenger RNA and protein levels. In addition, reintroduction of exogenous ATG5 or FIP200 partially reversed miR‐20a‐mediated autophagy inhibition under hypoxia. A negative correlation between miR‐20a and its target genes is observed in the hypoxic region of colon cancer tissues. Taken together, our findings suggest that hypoxia‐mediated autophagy was regulated by miR‐20a/ATG5/FI200 signaling pathway in CRC. miR‐20a‐mediated autophagy defect that might play an important role in hypoxia‐induced autophagy during colorectal tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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miR‐20a inhibits hypoxia‐induced autophagy by targeting ATG5/FIP200 in colorectal cancer

Che

Wang

Huang

et al. 2019

Molecular Carcinogenesis

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“…miR-20a, a member of miR-17-92 cluster, has already been widely studied in different cancers, acting as an oncogene in tumor development and progression (Chang et al, 2013;Liu et al, 2017;Wang et al, 2015;Weng et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance

Zhou

Zhang

et al. 2017

Preprint

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Multidrug resistance (MDR) significantly restricts the clinical efficacy of gastric cancer (GC) chemotherapy, and it is critical to search novel targets to predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that LRIG1 was overexpressed in chemo-sensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. We observed that up-regulation of LRIG1 enhanced chemo-sensitivity in GC cells. Interestingly, miR-20a, which was overexpressed in GC MDR cell lines and tissues, was identified to regulate LRIG1 expression by directly targeting its 3'untranslated region. We also found that inhibition of miR-20a suppressed GC MDR, and up-regulation showed opposite effects. Moreover, we demonstrated that the miR-20a/LRIG1 axis regulated GC cell MDR through EGFR mediated PI3K/AKT and MAPK/ERK signaling pathways. Finally, LRIG1 expression in human GC tissues is inversely correlated with miR-20a and EGFR. Taken together, the newly identified miR-20a/LRIG1/EGFR link provides insight into the MDR process of GC, and targeting this axis represents a novel potential therapeutic strategy to block GC chemo-resistance.

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“…MicroRNAs (miRNAs) are short, noncoding RNAs containing ;22 nt that predominantly interact with other genes by binding to complementary sequences in the 39 UTR of target mRNAs, thereby adversely regulating mRNA translation (15)(16)(17). Numerous studies have shown deregulation of miRNAs expression profiles in various diseases (18), including cancer (17,19,20). miRNAs play crucial roles in all physiologic and pathologic processes such as cell proliferation, apoptosis, invasion, and chemoresistance.…”

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Helicobacter pylori‐induced miR‐135b‐5p promotes cisplatin resistance in gastric cancer

et al. 2018

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Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression of miR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-κB. Treatment of gastric cancer cells with TNF-α induced miR-135b-5p in a NF-κB-dependent manner. Mechanistically, we found that miR-135b-5p targets Krüppel-like factor 4 (KLF4) and binds to its 3' UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection and miR-135b-5p-KLF4, suggesting that targeting miR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.-Shao, L., Chen, Z., Soutto, M., Zhu, S., Lu, H., Romero-Gallo, J., Peek, R., Zhang, S., El-Rifai, W. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer.

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MicroRNA-20a-mediated loss of autophagy contributes to breast tumorigenesis by promoting genomic damage and instability

Cited by 56 publications

References 55 publications

miR‐20a inhibits hypoxia‐induced autophagy by targeting ATG5/FIP200 in colorectal cancer

miR‐20a inhibits hypoxia‐induced autophagy by targeting ATG5/FIP200 in colorectal cancer

Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance

Helicobacter pylori‐induced miR‐135b‐5p promotes cisplatin resistance in gastric cancer

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