The novel role of circular RNA ST3GAL6 on blocking gastric cancer malignant behaviours through autophagy regulated by the FOXP2/MET/mTOR axis

Xu, Penghui; Zhang, Xing; Cao, Jiacheng; Yang, Jing; Chen, Zetian; Wang, Weizhi; Wang, Sen; Zhang, Lu; Xie, Li; Fang, Lang; Xia, Yiwen; Xuan, Zhe; Lv, Jialun; Xu, Hao; Xu, Zekuan

doi:10.1002/ctm2.707

Cited by 28 publications

(29 citation statements)

References 46 publications

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“…Our results showed that autophagy could be detected after KPT-330 treatment. Inhibition of the mTOR pathway has been reported to activate autophagy [42,43]. Our bioinformatic and western blot analyses veri ed that KPT-330 could induce mTOR-mediated autophagy.…”

Section: Discussionmentioning

confidence: 60%

Inhibition of XPO1 with KPT-330 induces autophagy-dependent apoptosis in gallbladder cancer by activating the p53/mTOR pathway

Zhao

Yang

Zhang

et al. 2022

Preprint

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Background Gallbladder cancer (GBC) is a highly aggressive malignant cancer in the biliary system with poor prognosis. XPO1 (chromosome region maintenance 1 or CRM1) mediates the nuclear export of several proteins, mainly tumor suppressors. Thus, XPO1 functions as a pro-oncogenic factor. KPT-330 (Selinexor) is a United States Food and Drug Administration approved selective inhibitor of XPO1 that demonstrates good therapeutic effects in hematologic cancers. However, the function of XPO1 and the effect of KPT-330 have not been reported in GBC. Methods We analyzed the correlation between XPO1 expression levels by q-PCR and clinical features of GBC patients. Cell proliferation assays were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT-330. mRNA sequencing was used to explore the underlying mechanisms. Western blot was performed to explore the relationship between apoptosis and autophagy. The in vivo antitumor effect of KPT-330 was investigated in a nude mouse model of gallbladder cancer. Results We found high expression of XPO1 was related to poor prognosis of GBC patients. We observed that XPO1 inhibitor KPT-330 the proliferation of GBC cells in vitro. Furthermore, XPO1 inhibitor KPT-330 induced apoptosis by reducing the mitochondrial membrane potential and autophagy in NOZ and GBC-SD cells. Indeed, KPT-330 led to nuclear accumulation of p53 and activated the p53/mTOR pathway to regulate autophagy-dependent apoptosis. Importantly, KPT-330 suppressed tumor growth with no obvious toxic effects in vivo. Conclusion XPO1 may be a promising prognostic indicator for GBC, and KPT-330 appears to be a potential drug for treating GBC effectively and safely.

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Section: Discussionmentioning

confidence: 60%

Inhibition of XPO1 with KPT-330 induces autophagy-dependent apoptosis in gallbladder cancer by activating the p53/mTOR pathway

Zhao

Yang

Zhang

et al. 2022

Preprint

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“…It also regulates autophagy and apoptosis, possibly through the repression of MET axis transcription by FOXP2. These results suggest that CircST3GAL6 may be a potential target for gastric cancer therapy 103 …”

Section: Lncrnas and Circrnas In Cancersmentioning

confidence: 74%

LncRNAs and CircRNAs in cancer

Yin

Lin

et al. 2022

MedComm

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It is well known that noncoding RNAs (ncRNAs) cannot encode proteins, but they can play important regulatory roles in tumors by combining with proteins, RNAs, and DNAs. As more and more studies reveal the important roles and underlying mechanisms of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in cancer, their huge application potential in cancer therapy cannot be ignored. For example, lncRNAs can be involved in tumor‐related signal transduction pathways, cell cycle control, DNA damage, epigenetic regulation, and microRNA control. A group of studies confirmed that abnormal expression of lncRNAs can affect cancer progression. Furthermore, as covalently closed continuous circular ncRNAs, many recent studies have shown that circRNAs have regulatory effects and other important biological significances in cancer. Interestingly, circRNAs were found to have translational functions. This has greatly attracted people's attention to circRNAs research. In this review, we introduce the important roles of lncRNAs and circRNAs in some representative cancers, respectively. Furthermore, we focus on the biological functions and important clinical therapeutic implications of lnRNAs and circRNAs in neuroblastoma. Our review also focuses on providing rationale and relevant references for novel biomarkers for neuroblastoma diagnosis, prognosis, and treatment.

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“…S3C-S3D) and five putative FOXP2 targets (Fig. S3E), such as MET and PIK3R1, identified by chromatin immunoprecipitation assays in both mice and humans [11,15,[47][48][49].…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in FOXP2 are the only known cause of developmental speech and language disorder in humans [11]. Most of the recent studies investigating the roles of FOXP2 in cancer have focused on noncoding RNA-mediated dysregulation of FOXP2, suggesting that FOXP2 has either oncogenic or tumorsuppressive effects on cancer development in different tumor contexts [12][13][14][15][16]. However, to date, little is known regarding the link between FOXP2 and prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted July 6, 2022. ; https://doi.org/10.1101/2022.07.06.498943 doi: bioRxiv preprint mediated dysregulation of FOXP2, suggesting that FOXP2 has either oncogenic or tumorsuppressive effects on cancer development in different tumor contexts [12][13][14][15][16]. However, to date, little is known regarding the link between FOXP2 and prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

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FOXP2confers oncogenic effects in prostate cancer through activating MET signalling

Zhu

Chen

Dong

et al. 2022

Preprint

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Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that FOXP2 is overexpressed in human prostate cancer cells and prostate tumors, but its expression is absent in normal prostate epithelial cells and low in benign prostatic hyperplasia. To date, little is known regarding the link of FOXP2 to prostate cancer. We observed that high FOXP2 expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of FOXP2 induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, FOXP2 knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of FOXP2 in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of FOXP2 aberrantly activates oncogenic MET signalling and inhibitors targeting MET signalling effectively reverts the FOXP2-induced oncogenic phenotype. Additionally, the novel recurrent FOXP2-CPED1 fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data demonstrate for the first time that FOXP2 is an oncogene involved in tumorigenicity of prostate.

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The novel role of circular RNA ST3GAL6 on blocking gastric cancer malignant behaviours through autophagy regulated by the FOXP2/MET/mTOR axis

Cited by 28 publications

References 46 publications

Inhibition of XPO1 with KPT-330 induces autophagy-dependent apoptosis in gallbladder cancer by activating the p53/mTOR pathway

Inhibition of XPO1 with KPT-330 induces autophagy-dependent apoptosis in gallbladder cancer by activating the p53/mTOR pathway

LncRNAs and CircRNAs in cancer

FOXP2confers oncogenic effects in prostate cancer through activating MET signalling

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