&lt;p&gt;MicroRNA-375 Targets ATG14 to Inhibit Autophagy and Sensitize Hepatocellular Carcinoma Cells to Sorafenib&lt;/p&gt;

Yang, Shuo; Wang, Minggang; Yang, Liang; Li, Yan; Ma, Yingbo; Peng, Xueqiang; Li, Xinyu; Li, Bowen; Jin, Hongyuan; Li, Hangyu

doi:10.2147/ott.s247655

Cited by 29 publications

(26 citation statements)

References 52 publications

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“…In another study, by transfecting miR‐375 mimic into Huh7 cells, a marked increase of apoptosis rate of Huh7 cells is observed 10 . Additionally, miR‐375 can enhance the sensitivity of HCC cells to sorafenib by the regulation of ATG14 expression 22 . In our current research, the inhibitory effect of miR‐375 on HCC development was further verified by using SNU‐398 and HepG2 cells, and we demonstrated that circ_0072088 contributed to the dysregulation of miR‐375 in HCC.…”

Section: Discussionmentioning

confidence: 94%

Circ_0072088 promotes progression of hepatocellular carcinoma by activating JAK2/STAT3 signaling pathway via miR‐375

Xiao

2021

IUBMB Life

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Circular RNAs feature prominently in cancer development. Nonetheless, the role of circ_0072088 in hepatocellular carcinoma (HCC) remains unclear. GEO databases (GSE97332, GSE108724, GSE36915, and GSE33006) were used to screen out the differentially expressed circRNAs, miRNAs, and mRNA in HCC. The expressions of circ_0072088, miR‐375, and Janus Kinase 2 (JAK2) mRNA in HCC tissue and cell lines were determined with quantitative real‐time polymerase chain reaction. RNase R treatment assay was used to measure the stability of circ_0072088, and subcellular fraction assay was used to detect the localization of circ_0072088. Cell counting kit‐8 assay, flow cytometry, and Transwell assay were used to measure proliferation, apoptosis, migration, and invasion of HCC cells. RNA immunoprecipitation and dual‐luciferase reporter gene assay were employed for investigating the binding sequence between circ_0072088 and miR‐375, as well as miR‐375 and JAK2 3′UTR. Western blot assay was used to detect the expression of JAK2 and p‐STAT3 after circ_0072088 and miR‐375 were selectively regulated. Circ_0072088 and JAK2 mRNA expressions were highly expressed in HCC tissues and cell lines while miR‐375 expression was remarkably downregulated. Circ_0072088 was resistant to RNase R treatment and mainly located in the cytoplasm of HCC cells. The transfection of circ_0072088 overexpression plasmid or miR‐375 inhibitors promoted the proliferation, migration, and invasion, and inhibited the apoptosis of HCC cells, whereas transfection of circ_0072088 siRNA or miR‐375 mimics exerted opposite effects. Besides, miR‐375 was confirmed as a target of circ_0072088 and miR‐375 could further downregulate the expression of JAK2. MiR‐375 mimics could reverse the upregulation of JAK2 and p‐STAT3 protein induced by circ_0072088 overexpression. Circ_0072088 can enhance the proliferation, migration, and invasion, and impede apoptosis of HCC cells. Mechanistically, circ_0072088 activates JAK2/STAT3 signaling pathway by serving as a molecular sponge of miR‐375.

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Section: Discussionmentioning

confidence: 94%

Circ_0072088 promotes progression of hepatocellular carcinoma by activating JAK2/STAT3 signaling pathway via miR‐375

Xiao

2021

IUBMB Life

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“…The assistance of miR-375 in anti-tumor therapy has already been uncovered. MiR-375 augmented the susceptibility of HCC cells to sorafenib by targeting the autophagy-related gene, ATG14 [17]. MiR-375 also inhibited the survival of fulvestrant-resistant breast cancer cells by restraining autophagy [18].…”

Section: Discussionmentioning

confidence: 99%

MiR-375 gene therapy attenuates drug resistance of hepatocellular carcinoma cells by inhibiting cell autophagy

Wang

Yang

2020

Preprint

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Objective To probe into the regulatory mechanism of miR-375 in hepatocellular carcinoma (HCC) cells under sorafenib treatment. Methods Western blotting and qRT-PCR were applied to measure the expressions of miR-375 and SIRT5 in parental HCC cells (HepG2 and Huh7) and sorafenib-resistant HCC cells (HepG2/so and Huh7/so). HepG2/so cells were accordingly transfected with miR-375 mimic, miR-375 inhibitor, sh-SIRT5, pcDNA3.1-SIRT5 or negative control. Western blotting measured the expressions of p62, LC3I and LC3II in HCC cells. CCK-8 and flow cytometry assessed the survivability and apoptosis of HCC cells, respectively. Bioinformatics techniques and dual-luciferase reporter assay predicted and verified the targeting relationship between miR-375 and SIRT5. Results MiR-375 was under-expressed and SIRT5 was over-expressed in HCC cells. Autophagy inhibitor impaired the survival of HepG2/so cells transfected with miR-375 inhibitor. Autophagy activator enhanced the drug resistance of HepG2/so cells transfected with miR-375 mimic. MiR-375 suppressed the drug resistance of HepG2/so cells by inhibiting autophagy. SIRT5 enhanced the drug resistance of HepG2/so cells by promoting autophagy and it could be targeted by miR-375. Conclusion MiR-375 suppresses autophagy to attenuate the drug resistance of HCC cells by regulating SIRT5. The findings of this study may provide new therapeutic targets for treating hepatocellular carcinoma.

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“…This blunted autophagy response contributes to increased susceptibility of HCC cell lines and xenograft models to hypoxic stress. In a similar trend, the same miR-375 blocks ATG14-mediated autophagy in sorafenib-treated Huh7 and HepG2 cells and increase sensitivity to sorafenib [ 8 , 91 ]. In another study, overexpression of miR-132 in HCC cells and tissues blocks PIK3R3-dependent autophagy but promotes apoptosis.…”

Section: Ageingmentioning

confidence: 95%

Regulation of autophagy by miRNAs in human diseases

Roy

2021

Nucleus

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Autophagy is a homeostatic process designed to eliminate dysfunctional and aging organelles and misfolded proteins through a well-concerted pathway, starting with forming a double-membrane vesicle and culminating in the lysosomal degradation of the cargo enclosed inside the mature vesicle. As a vital sentry of cellular health, autophagy is regulated in every human disease condition and is an essential target for non-coding RNAs like microRNAs (miRNAs). miRNAs are short oligonucleotides that specifically bind to the 3'-untranslated region (UTR) of target mRNAs, thus leading to mRNA silencing, degradation, or translation blockage. This review summarizes the recent findings regarding the regulation of autophagy and autophagy-related genes by different miRNAs in various pathological conditions, including cancer, kidney and liver disorders, neurodegeneration, cardiovascular disorders, infectious diseases, aging-related conditions, and inflammation-related diseases. As miRNAs are being identified as prime regulators of autophagy in human disease, pharmacological molecules and traditional medicines targeting these miRNAs are also being tested in disease models, thus initiating a new series of therapeutic interventions targeting autophagy.

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<p>MicroRNA-375 Targets ATG14 to Inhibit Autophagy and Sensitize Hepatocellular Carcinoma Cells to Sorafenib</p>

Cited by 29 publications

References 52 publications

Circ_0072088 promotes progression of hepatocellular carcinoma by activating JAK2/STAT3 signaling pathway via miR‐375

Circ_0072088 promotes progression of hepatocellular carcinoma by activating JAK2/STAT3 signaling pathway via miR‐375

MiR-375 gene therapy attenuates drug resistance of hepatocellular carcinoma cells by inhibiting cell autophagy

Regulation of autophagy by miRNAs in human diseases

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