Down-regulation of OGT promotes cisplatin resistance by inducing autophagy in ovarian cancer

Zhou, Fuxing; Yang, Xianghua; Zhao, Hang; Liu, Yu; Feng, Yunjiang; An, Rui; Lv, Xiaohui; Li, Jia; Chen, Biliang

doi:10.7150/thno.27806

Cited by 110 publications

(88 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Briefly, autophagy is a highly conserved cellular process during evolution, which is induced by diverse pathologies and cellular stresses containing nutrient deprivation, endoplasmic reticulum stress, and hypoxia 17 . Autophagy has also been involved in cancer resistance to multiple chemotherapeutic drugs, including cisplatin 18 , paclitaxel 19 , and gemcitabine 20 . Autophagy plays a vital role in regulating colorectal cancer chemoresistance, blocking of which will be developed as a promising therapy strategy for colorectal cancer treatment 21 .…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

et al. 2020

View full text Add to dashboard Cite

Trastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer, but its efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. In this study, publicly available expression profiling data from breast cancer and bioinformatics analyses were used to screen potential miRNAs in trastuzumab resistance. A series of gain-or loss-functional assays were performed to define the function of miR-567 and ATG5 in trastuzumab resistance and autophagy, both in vitro and in vivo. Our results showed that miR-567 was significantly decreased in trastuzumab-resistant patients compared with responding patients. Moreover, miR-567 was also downregulated in trastuzumab-resistant cells compared with parental cells. Overexpression of miR-567 reversed chemoresistance, whereas silence of miR-567 induced trastuzumab resistance, both in vitro and in vivo. In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.

show abstract

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…PBK promotes the metastasis of serous ovarian carcinoma and confers cisplatin resistance [17]. OGT was downregulated in ovarian cancer, which in turn, promotes cisplatin resistance by inducing autophagy [18]. The previous studies found that MARCH5 and PKP3 regulated the autophagy and invasion of ovarian cancer [7, 19].…”

Section: Discussionmentioning

confidence: 99%

ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2

Zhu

Gan

Jiang

et al. 2019

J Exp Clin Cancer Res

189

169

View full text Add to dashboard Cite

Background ALKBH5 regulated the malignant behavior of breast cancer and glioblastoma. However, the expression and function of ALKBH5 in epithelial ovarian cancer have not yet been determined. In the present study, we investigated the expression and function of ALKBH5 in epithelial ovarian cancer with respect to its potential role in the tumorigenesis of the disease as well as an early diagnostic marker. Methods Immunohistochemistry and western blot were used to detect protein expression. Gene silencing and over-expression experiment were used to study gene function. Cell proliferation assay and Matrigel invasion assays were used to detect cell proliferation and invasion, respectively. The nude mouse tumor formation experiment was used to evaluate the growth of cells in vivo. Results The expression of ALKBH5 was found to be increased in epithelial ovarian cancer tissue as compared to the normal ovarian tissues. The silencing of ALKBH5 in SKOV3 cells enhanced the autophagy and inhibited the proliferation and invasion in vitro and in vivo, whereas the ectopic expression of ALKBH5 in A2780 cells exerted an opposite effect. Mechanical study revealed that ALKBH5 physically interacted with HuR. ALKBH5 activated EGFR-PIK3CA-AKT-mTOR signaling pathway. Also, ALKBH5 enhanced the stability of BCL-2 mRNA and promoted the interaction between Bcl-2 and Beclin1. Conclusion Overall, the present study identified ALKBH5 as a candidate oncogene in epithelial ovarian cancer and a potential target for ovarian cancer therapy. Electronic supplementary material The online version of this article (10.1186/s13046-019-1159-2) contains supplementary material, which is available to authorized users.

show abstract

“…A recent study on the role of OGT in the liver revealed that phosphorylated OGT can promote O-GlcNAc modification and activate Ulk proteins by potentiating AMPK-dependent phosphorylation, and that ablation of OGT could reduce autophagic flux [16]. In ovarian cancer cells downregulation of OGT induces cell autophagy through O-GlcNAc modification of SNAP-29, which contributes to cisplatin resistance [22]. OGT has also been found to regulate bladder cancer cell autophagy.…”

Section: Validationmentioning

confidence: 99%

O-GlcNAcylation promotes malignant phenotypes of bladder cancer cells

Jin¹,

Lu²,

Dai³

et al. 2020

neo

View full text Add to dashboard Cite

O-GlcNAcylation (O-GlcNAc) is a posttranslational modification that is mediated by O-GlcNAc-transferase (OGT) and reversed by O-GlcNAcase (OGA). Increasing evidence indicates that protein O-GlcNAcylation is increased in various types of cancer. In the present study, we aimed to evaluate the expression and function of both OGT and OGA in bladder cancer cells in vitro and in vivo. Expression data of OGT and OGA at the mRNA level was obtained from the Oncomine database. Effects of OGT and OGA on cell proliferate, invasive and migratory abilities were assessed using MTT, wound healing, cell invasive assay, and cell cycle analysis. In vivo assay was also performed in nude mice. The results revealed that the expression of OGT in bladder cancer tissues is higher than that of normal tissues, while the OGA level was found to be lower in cancer tissues. We also found that knockdown of OGT could inhibit cell proliferation, migration, invasion, and induce cell cycle arrest, while these are reversed when OGA is inhibited. We also observed that O-GlcNAcylation could promote tumor formation in vivo, compared with negative control. In summary, this study describes the oncogenic role of O-GlcNAcylation in bladder cancer cells.

show abstract

Down-regulation of OGT promotes cisplatin resistance by inducing autophagy in ovarian cancer

Cited by 110 publications

References 46 publications

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

RETRACTED ARTICLE: Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer

ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2

O-GlcNAcylation promotes malignant phenotypes of bladder cancer cells

Contact Info

Product

Resources

About