Egr-1 promotes hypoxia-induced autophagy to enhance chemo-resistance of hepatocellular carcinoma cells

Peng, Wan-Xin; Xiong, Erhui; Ge, Lu; Wan, Yan-ya; Zhang, Chunli; Du, F.; Xu, Min; Bhat, Reyaz Ahmed; Jin, Jie; Gong, Aihua

doi:10.1016/j.yexcr.2015.12.006

Cited by 45 publications

(43 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[22][23][24][25] EGR1 plays complicated roles in HCC. Several studies have stated that EGR1 is overexpressed in HCC tissues, enhances drug resistance by promoting hypoxia-induced autophagy 26 and accelerates the progression of HCC; [27][28][29] however, data from several independent laboratories have demonstrated that EGR1 inhibits HCC cell motility and invasion. [30][31][32] In our present study, we found that CD24A was the predominant CD24 isoform in HCC and plays a major role in cell proliferation, migration, and invasion.…”

Section: Introductionmentioning

confidence: 99%

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

Li¹,

Chen²,

Ge³

et al. 2019

OTT

View full text Add to dashboard Cite

Introduction: CD24 is known as a heavily glycosylated cell surface molecule that is highly expressed in a wide variety of human malignancies. Previous studies have shown that CD24 plays an important role in self-renewal, proliferation, migration, invasion and drug resistance of hepatocellular carcinoma (HCC). However, little is known about the expression and function of CD24 isoform a (CD24A) and CD24 isoform b (CD24B) in HCC. Materials and methods: Quantitative real-time polymerase chain reaction (qPCR) and Western blotting were performed to detect CD24 and EGR1 expression in HCC cells and tissue. The function of CD24 in cell proliferation was verified with MTT assays, colony formation assays and tumor xenograft models. Wound healing assays and invasion assays were performed to clarify the function of CD24 in the regulation of cell migration and invasion in HCC. A dual luciferase reporter assay and chromatin immunoprecipitation assay were used to analyze the regulation mechanism of CD24A. Results: CD24A but not CD24B, which was barely detected by qPCR and Western blotting, is significantly upregulated in HCC tissue. Both CD24A and CD24B contribute to HCC cell proliferation, migration and invasion, but CD24A is more effective than CD24B. EGR1 downregulates CD24A and exerts transcription-promoting activity on the CD24A promoter. Furthermore, EGR1 represses HCC cell proliferation via downregulation of CD24A. Conclusion: CD24A is the predominant CD24 isoform in HCC and plays a major role in cell proliferation, migration, and invasion. EGR1 can exert its antitumor effect through transcriptional downregulation of CD24A in HCC.

show abstract

Section: Introductionmentioning

confidence: 99%

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

Li¹,

Chen²,

Ge³

et al. 2019

OTT

View full text Add to dashboard Cite

show abstract

“…EGR1 is an immediate-early response gene, of which its expression can be induced within minutes after stimulation [30]. Mitogens [31,32], growth factors [33], and stress stimuli, such as cigarette smoke [34–36], hypoxia [37,38], and nutrient deprivation [39] regulate EGR1. For example, in agreement with our data, glucose restriction rapidly increases EGR1 protein levels in multiple cell lines [39].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

et al. 2018

View full text Add to dashboard Cite

Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes. These transcriptional changes are reflected at the epigenetic level (H3K4me3, H3K27ac, and H3K56ac) and are independent of autophagic flux. As a proof of principle that this resource can be used to identify novel autophagy regulators, we followed up on one identified target: EGR1 (early growth response 1), which indeed appears to be a central transcriptional regulator of autophagy by affecting autophagy-associated gene expression and autophagic flux. Taken together, these data stress the relevance of transcriptional and epigenetic regulation of autophagy and can be used as a resource to identify (novel) factors involved in autophagy regulation.

show abstract

“…Peng et al showed that early growth response gene-1 (Erg-1) transcriptionally regulates hypoxia-induced autophagy by binding to LC3 promoter in HCC cells and enhanced cisplatin and epirubicin resistance. [70] Similarly, ATF4 being transcriptional regulator of the cellular hypoxic response to the UPR also showed resistance to bortezomib which actually a UPR-apoptosis mediator through autophagy induction as a survival key in HCC. [71] Inhibition of these transcriptional regulator increased chemosensitivity representing an attractive therapeutic approach.…”

Section: Resistance To Chemotherapymentioning

confidence: 99%

Hypoxia-induced autophagy in hepatocellular carcinoma and anticancer therapy

Kabir¹,

Yong²

2017

Natl J Physiol Pharm Pharmacol

View full text Add to dashboard Cite

Autophagy is a genetically programmed dynamic process for the lysosomal degradation and recycling of bulk cytoplasmic contents, abnormal proteins, and damaged organelles. Along with cellular homeostasis maintenance, autophagy plays a fundamental role in cancer as tumor cells activate autophagy under stressful conditions such as hypoxia, nutrient derivation, and anticancer therapy. Increasing reports suggest the protective role of autophagy in hepatocellular carcinoma (HCC). Despite recent developments in HCC anticancer treatment, the overall patient survival remains poor. Tumor hypoxia, a common characteristic of most solid tumors like HCC is correlated with poor prognosis for patients partly because hypoxia promotes resistance to cancer therapy. Hypoxia preferentially selects apoptosis-resistant cells and activates autophagy as a survival mechanism leading to malignant and aggressive phenotype. In this review, we summarized the molecules involved in hypoxia-induced autophagy for HCC progression and anticancer therapy resistance. In addition, the molecular pathways involved in hypoxia-induced autophagy were provided. We also focused on some recent researches between hypoxia-induced autophagy and microRNAs in HCC. We believe understanding the novel function of hypoxia-regulated autophagy may coin new targets for the betterment of HCC treatment and improved clinical outcomes.

show abstract

Egr-1 promotes hypoxia-induced autophagy to enhance chemo-resistance of hepatocellular carcinoma cells

Cited by 45 publications

References 45 publications

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

Hypoxia-induced autophagy in hepatocellular carcinoma and anticancer therapy

Contact Info

Product

Resources

About