PAQR3 suppresses the growth of non-small cell lung cancer cells via modulation of EGFR-mediated autophagy

Cao, Qianqian; You, Xu; Xu, Liang; Wang, Lin; Yan, Chen

doi:10.1080/15548627.2019.1659654

Cited by 56 publications

(39 citation statements)

References 39 publications

(61 reference statements)

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“…Recently, autophagy has emerged as a promising target for cancer treatment, and induction of autophagyassociated cytotoxic death through blockade of autophagic flux has been increasingly recognized as a novel cancer therapeutic strategy [19][20][21]. In the present study, we indicated that ARCSP has an effective antitumor effect on cervical cancer cells.…”

Section: Discussionmentioning

confidence: 50%

Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway

Yang

Wang

Song

et al. 2020

J Exp Clin Cancer Res

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Background Autophagy is an intracellular process through which intracellular components are recycled in response to nutrient or growth factor deficiency to maintain homeostasis. We identified the peptide autophagy-related cancer-suppressing peptide (ARCSP), a potential antitumor peptide that disrupts intracellular homeostasis by blocking autophagic flux and causes cytotoxic death. Methods The proliferative ability of ARCSP-treated cervical cancer cells was examined by the CCK8, EdU, and colony formation assays. The TUNEL assay was used to detect apoptosis. Mitochondrial function was evaluated based on the mitochondrial membrane potential. Autophagic flux was detected by immunofluorescence and confocal microscopy. The autophagy-related proteins AMPK, Raptor, mTOR, p62, LC3B, atg7, Rab7, LAMP1, LAMP2, and cathepsin D were detected by Immunoblotting. The antitumor effect of ARCSP was explored in vivo by establishing a transplant tumor model in nude mice. Results The results demonstrated that ARCSP induced cell death and inhibited proliferation. ARCSP induced AMPK/mTOR activation, resulting in the accumulation of the proteins LC3B, p62 and Atg7. ARCSP also blocked autophagosome-lysosome fusion by inhibiting endosomal maturation and increasing the lysosomal pH. The accumulation of nonfused autophagosomes exacerbated cytotoxic death, whereas knocking down Atg7 reversed the cytotoxic death induced by ARCSP. ARCSP-treated cells exhibited increased cytotoxic death after cotreatment with an autophagy inhibitor (Chloroquine CQ). Furthermore, the tumors of ARCSP-treated nude mice were significantly smaller than those of untreated mice. Conclusions Our findings demonstrate that ARCSP, a novel lethal nonfused autophagosome inducer, might cause mitochondrial dysfunction and autophagy-related cytotoxic death and is thus a prospective agent for cancer therapy.

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Section: Discussionmentioning

confidence: 50%

Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway

Yang

Wang

Song

et al. 2020

J Exp Clin Cancer Res

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“…Cell proliferation assay CCK-8 is a widely used method for detecting cell proliferation [19]. Ten hours after the cell damage, 10 μl Cell Counting Kit-8 (CCK-8) (Biosharp Life Sciences, Hefei, China) reagent was added to each well, and the optical density was measured at 450 nm.…”

Section: E920855-2mentioning

confidence: 99%

Protective effect of BMSCs-derived exosomes mediated by BDNF on TBI via miR-216a-5p

Jia

et al. 2020

Med Sci Monit

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Background: Transplantation of exosomes derived from mesenchymal stem cells (MSCs-Exo) can improve the recovery of neurological function in rats after traumatic brain injury (TBI). We tested a new hypothesis that brain-derived neurotrophic factor (BDNF)-induced MSCs-Exo can effectively promote functional recovery and neurogenesis in rats after TBI. Material/Methods: BM-MSCs of rats were extracted by whole bone marrow culture, BDNF was added to BM-MSCs as an intervention, supernatant was collected, and exosomes were separated and purified by ultracentrifugation. Exosomes were identified by Western blot (WB), transmission electron microscopy (TEM), and particle size analysis and were subsequently used in cell and animal experiments. The experimental animals were divided into a sham group, a PBS group, an MSCs-Exo group, and a BDNF-induced MSCs-Exo group (n=12). An electric cortical contusion impactor (eCCI) was used to cause TBI in all rats except the sham group. We investigated the recovery of sensorimotor function and spatial learning ability, inflammation inhibition, and neuron regeneration in rats after TBI. Results: Compared with the MSCs-Exo group, the BDNF-induced MSCs-Exo group showed better effects in promoting the recovery of sensorimotor function and spatial learning ability. BDNF-induced MSCs-Exo successfully inhibited inflammation and promoted neuronal regeneration in vivo and in vitro. We further analyzed miRNAs in BDNF-induced MSCs-Exo and MSCs-Exo and found that the expression of miR-216a-5p in BDNF-induced MSCs-Exo was significantly higher than that in MSCs-Exo as determined by qRT-PCR. Rescue experiments indicated that miR-216a-5p had a similar function as BDNF-induced MSCs-Exo. Conclusions: We found that BDNF-induced MSCs-Exo can improve cell migration and inhibit apoptosis better than MSCs-Exo in rats after TBI, and the mechanism may be related to the high expression of miR-216a-5p.

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“…Growing evidence indicates a close correlation between autophagy and lung cancer. PAQR3 was demonstrated to suppress the tumor progression of NSCLC cells by modulating EGFR-regulated autophagy [25]. The downregulation of autophagy facilitated the anti-LUAD efficacy of Shh pathway suppression, thus highlighting a potential approach for LUAD therapy [26].…”

Section: Discussionmentioning

confidence: 98%

A Robust Signature Based on Autophagy-Associated LncRNAs for Predicting Prognosis in Lung Adenocarcinoma

Zhou

Shao

Dai

et al. 2020

BioMed Research International

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Objective. To construct a predictive signature based on autophagy-associated lncRNAs for predicting prognosis in lung adenocarcinoma (LUAD). Materials and Methods. Differentially expressed autophagy genes (DEAGs) and differentially expressed lncRNAs (DElncRNAs) were screened between normal and LUAD samples at thresholds of ∣log2Fold Change∣>1 and P value < 0.05. Univariate Cox regression analysis was conducted to identify overall survival- (OS-) associated DElncRNAs. The total cohort was randomly divided into a training group (n=229) and a validation group (n=228) at a ratio of 1 : 1. Multivariate Cox regression analysis was used to build prognostic models in the training group that were further validated by the area under curve (AUC) values of the receiver operating characteristic (ROC) curves in both the validation and total cohorts. Results. A total of 30 DEAGs and 2997 DElncRNAs were identified between 497 LUAD tissues and 54 normal tissues; however, only 1183 DElncRNAs were related to the 30 DEAGs. A signature consisting of 13 DElncRNAs was built to predict OS in lung adenocarcinoma, and the survival analysis indicated a significant OS advantage of the low-risk group over the high-risk group in the training group, with a 5-year OS AUC of 0.854. In the validation group, survival analysis also indicated a significantly favorable OS for the low-risk group over the high-risk group, with a 5-year OS AUC of 0.737. Univariate and multivariate Cox regression analyses indicated that only positive surgical margin (vs negative surgical margin) and high-risk group (vs low-risk group) based on the predictive signature were independent risk factors predictive of overall mortality in LUAD. Conclusions. This study investigated the association between autophagy-associated lncRNAs and prognosis in LUAD and built a robust predictive signature of 13 lncRNAs to predict OS.

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PAQR3 suppresses the growth of non-small cell lung cancer cells via modulation of EGFR-mediated autophagy

Cited by 56 publications

References 39 publications

Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway

Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway

Protective effect of BMSCs-derived exosomes mediated by BDNF on TBI via miR-216a-5p

A Robust Signature Based on Autophagy-Associated LncRNAs for Predicting Prognosis in Lung Adenocarcinoma

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