MiR-146b inhibits autophagy in prostate cancer by targeting the PTEN/Akt/mTOR signaling pathway

Gao, Song; Zhao, Zhiying; Wu, Rong; Wu, Lina; Tian, Xin; Zhang, Zhenyong

doi:10.18632/aging.101534

Cited by 40 publications

(28 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decline in Pink1 expression was also observed in the nuclei and cytoplasm of the RGC layer of aging retinas [42] (Figure 4F). Microtubule-associated protein 1B light chain 3B (LC3B) is a marker of autophagy, and the ratio of LC3B short segment (LC3B-II) to LC3B long segment (LC3B-I) is representative of the level of autophagy [43]. Consistent with decreased mitophagy, there was also a significant decrease in the LC3B-II/LC3B-I ratio in aging versus young retinas, suggesting a decrease in overall autophagy levels (Figure 4D, E).…”

Section: Resultsmentioning

confidence: 99%

Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina

Wang

Luo

Jin

et al. 2019

Aging

104

View full text Add to dashboard Cite

It is currently believed that aging is closely linked with mitochondrial dysfunction, and that resveratrol exhibits anti-aging and neuroprotective effects by improving mitochondrial function, even though the mechanisms are not well defined. This study explored mitochondrial quality (mitochondrial DNA integrity and copy number), mitochondrial function (fusion/fission, mitophagy/autophagy), antioxidant system and activity of the Akt/mTOR and Ampk/Sirt1/Pgc1α pathways, and inflammation in aging zebrafish retinas to identify the probable mechanisms of resveratrol’s anti-aging and neuroprotective effects. mtDNA integrity, mtDNA copy number, mitochondrial fusion regulators, mitophagy, and antioxidant-related genes were all decreased whereas Akt/mTOR activity and inflammation was increased upon aging in zebrafish retinas. Resveratrol was shown to not only increase mitochondrial quality and function, but also to suppress Akt/mTOR activity in zebrafish retinas. These results support the notion that mitochondrial dysfunction and increased Akt/mTOR activity are major players in age-related retinal neuropathy in zebrafish, and demonstrate a trend towards mitochondrial fragmentation in the aging retina. Importantly, resveratrol promoted mitochondrial function, up-regulating Ampk/Sirt1/Pgc1α, and down-regulated Akt/mTOR pathway activity in zebrafish retinas, suggesting that it may be able to prevent age-related oculopathy.

show abstract

Section: Resultsmentioning

confidence: 99%

Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina

Wang

Luo

Jin

et al. 2019

Aging

104

View full text Add to dashboard Cite

show abstract

“…A recent study reported that overexpression of miR-146b in breast cancer cells downregulated epidermal growth factor receptor expression, inhibited invasion and migration in vitro , and suppressed experimental lung metastasis in vivo , 8 suggesting that miR-146b serves as a tumor suppressor. However, some studies reported that miR-146b might act as an oncogene to promote proliferation, migration, and invasion of colorectal and prostate cancers 9, 10. Despite the fact that surging studies of the biogenesis and mechanisms of miR-146b were involved in the pathogenesis of multiple tumors, the accurate expression level and mechanistic function of miR-146b in bladder cancer remain unclear.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-146b Overexpression Promotes Human Bladder Cancer Invasion via Enhancing ETS2-Mediated mmp2 mRNA Transcription

Zhu¹,

Xu²,

Ruan

et al. 2019

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Although microRNAs have been validated to play prominent roles in the occurrence and development of human bladder cancer (BC), alterations and function of many microRNAs (miRNAs) in bladder cancer invasion are not fully explored yet. miR-146b was reported to be a tumor suppressor or oncomiRNA in various types of cancer. However, its accurate expression, function, and mechanism in bladder cancer remain unclear. Here we discovered that miR-146b was frequently upregulated in bladder cancer tissues compared with adjacent non-cancerous tissues. Inhibition of miR-146b resulted in a significant inhibitory effect on the invasion of bladder cancer cells by reducing mmp2 mRNA transcription and protein expression. We further demonstrated that knockdown of miR-146b attenuated ETS2 expression, which was the transcription factor of matrix metalloproteinase (MMP)2. Moreover, mechanistic studies revealed that miR-146b inhibition stabilized ARE/poly(U)-binding/degradation factor 1 ( auf1) mRNA by directly binding to its mRNA 3′ UTR, further reduced ets2 mRNA stability, and finally inhibited mmp2 transcription and attenuated bladder cancer invasion abilities. The identification of the miR-146b/AUF1/ETS2/MMP2 mechanism for promoting bladder cancer invasion provides significant insights into understanding the nature of bladder cancer metastasis. Targeting the pathway described here may be a novel approach for inhibiting invasion and metastasis of bladder cancer.

show abstract

“…There are various cellular signalling pathways regulating autophagy, including mTOR, PTEN and AMPK (Zhou et al, 2013;Liu et al, 2018a;Tomas-Hernández et al, 2018). Among them, mTOR signaling pathway is the most important mechanism (Zhou et al, 2013;Gao et al, 2018;Liu et al, 2018b). Our results showed that MAN treatment decreased the expression levels of phosphorylated-AKT, -mTOR, and -S6 ( Figure 3G), demonstrating that AKT/mTOR pathway is responsible for MAN-triggered autophagy.…”

Section: Discussionmentioning

confidence: 70%

A Novel Benzofuran Derivative Moracin N Induces Autophagy and Apoptosis Through ROS Generation in Lung Cancer

Gao

Sun

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Introduction: The leaves of Morus alba L is a traditional Chinese medicine widely applied in lung diseases. Moracin N (MAN), a secondary metabolite extracted form the leaves of Morus alba L, is a potent anticancer agent. But its molecular mechanism remains unveiled. Objective: In this study, we aimed to examine the effect of MAN on human lung cancer and reveal the underlying molecular mechanism. Methods: MTT assay was conducted to measure cell viability. Annexin V-FITC/PI staining was used to detect cell apoptosis. Confocal microscope was performed to determine the formation of autophagosomes and autolysosomes. Flow cytometry was performed to quantify cell death. Western blotting was used to determine the related-signaling pathway. Results: In the present study, we demonstrated for the first time that MAN inhibitd cell proliferation and induced cell apoptosis in human non-small-cell lung carcinoma (NSCLC) cells. We found that MAN treatment dysregulated mitochondrial function and led to mitochondrial apoptosis in A549 and PC9 cells. Meanwhile, MAN enhanced autophagy flux by the increase of autophagosome formation, the fusion of autophagsomes and lysosomes and lysosomal function. Moreover, mTOR signaling pathway, a classical pathway regualting autophagy, was inhibited by MAN in a time-and dose-dependent mannner, resulting in autophagy induction. Interestingly, autophagy inhibition by CQ or Atg5 knockdown attenuated cell apoptosis by MAN, indicating that autophagy serves as cell death. Furthermore, autophagy-mediated cell death by MAN can be blocked by reactive oxygen species (ROS) scavenger NAC, indicating that ROS accumulation is the inducing factor of apoptosis and autophagy. In summary, we revealed the molecular

show abstract

MiR-146b inhibits autophagy in prostate cancer by targeting the PTEN/Akt/mTOR signaling pathway

Cited by 40 publications

References 45 publications

Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina

Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina

MicroRNA-146b Overexpression Promotes Human Bladder Cancer Invasion via Enhancing ETS2-Mediated mmp2 mRNA Transcription

A Novel Benzofuran Derivative Moracin N Induces Autophagy and Apoptosis Through ROS Generation in Lung Cancer

Contact Info

Product

Resources

About