RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-κB pathways

Huang, Lei; Jian, Zhiyuan; Gao, Yi; Zhou, Ping; Zhang, Gan; Jiang, Bin; Lv, Yi

doi:10.18632/aging.102167

Cited by 42 publications

(36 citation statements)

References 48 publications

(49 reference statements)

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“…The activation of STAT3 plays a vital role in mediating anti-apoptosis genes to suppress cell apoptosis, including MCL1 (Bhattacharya et al, 2005). It was reported that activation of STAT3 suppressed cell apoptosis, and promoted cell migration and invasion, cell cycle arrest by modulating several genes' expression in liver, ovarian and colon cancer (Bhattacharya et al, 2005;Chung et al, 1997;Huang et al, 2019). In our study, we found that RPN2 overexpression enhanced the phosphorylation levels STAT3 and promoted its nuclear translocation ( Fig.…”

Section: Discussionsupporting

confidence: 54%

Overexpression of RPN2 suppresses radiosensitivity of glioma cells by activating STAT3 signal transduction

Ran

Song

et al. 2020

Mol Med

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Background: Radiation therapy is the primary method of treatment for glioblastoma (GBM). Therefore, the suppression of radioresistance in GBM cells is of enormous significance. Ribophorin II (RPN2), a protein component of an N-oligosaccharyl transferase complex, has been associated with chemotherapy drug resistance in multiple cancers, including GBM. However, it remains unclear whether this also plays a role in radiation therapy resistance in GBM. Methods: We conducted a bioinformatic analysis of RPN2 expression using the UCSC Cancer Genomics Browser and GEPIA database and performed an immunohistochemical assessment of RPN2 expression in biopsy specimens from 34 GBM patients who had received radiation-based therapy. We also studied the expression and function of RPN2 in radiation-resistant GBM cells. Results: We found that RPN2 expression was upregulated in GBM tumors and correlated with poor survival. The expression of RPN2 was also higher in GBM patients with tumor recurrence, who were classified to be resistant to radiation therapy. In the radiation-resistant GBM cells, the expression of RPN2 was also higher than in the parental cells. Depletion of RPN2 in resistant cells can sensitize these cells to radiation-induced apoptosis, and overexpression of RPN2 had the reverse effect. Myeloid cell leukemia 1 (MCL1) was found to be the downstream target of RPN2, and contributed to radiation resistance in GBM cells. Furthermore, STAT3 was found to be the regulator of MCL1, which can be activated by RPN2 dysregulation. Conclusion: Our study has revealed a novel function of RPN2 in radiation-resistant GBM, and has shown that MCL1 depletion or suppression could be a promising method of therapy to overcome the resistance promoted by RPN2 dysregulation.

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Section: Discussionsupporting

confidence: 54%

Overexpression of RPN2 suppresses radiosensitivity of glioma cells by activating STAT3 signal transduction

Ran

Song

et al. 2020

Mol Med

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“…STAT3 plays a role in promoting the invasive capacities of HCC cells by regulating the expression of MMPs, such as MMP-2 and MMP-9 [36,59]. Secreted MMPs cleave the extracellular matrix in the tumor microenvironment, removing the physical barrier for cancer cells to invade into the surrounding tissue.…”

Section: Stat3 In Invasion and Metastasismentioning

confidence: 99%

JAK/STAT signaling in hepatocellular carcinoma

et al. 2020

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Liver cancer is the second most lethal cancer in the world with limited treatment options. Hepatocellular carcinoma (HCC), which accounts for more than 80% of all liver cancers, has had increasing global incidence over the past few years. There is an urgent need for novel and better therapeutic intervention for HCC patients. The JAK/STAT signaling pathway plays a multitude of important biological functions in both normal and malignant cells. In a subset of HCC, JAK/STAT signaling is aberrantly activated, leading to dysregulation of downstream target genes that controls survival, angiogenesis, stemness, immune surveillance, invasion and metastasis. In this review, we will focus on the role of JAK/STAT signaling in HCC and discuss the current clinical status of several JAK/STAT inhibitors.

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“…The self-protection mechanism of autophagy occurs in unfavorable environment, which is closely related to the occurrence and development of tumor [8]. For instance, autophagy can affect the progression of HCC by regulating the expression of other factors or signaling pathways, such as RAC1, NF-κB, and PI3K pathways [9][10][11]. However, the specific molecular mechanism between HCC and autophagy remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy

Hong

Gao

et al. 2020

World J Surg Onc

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Background: Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC and to explore its related mechanisms. Methods: The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cell apoptosis was induced by nutrient-deficient culture medium and detected by Cell Counting Kit-8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection. Results: HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage, and lymph node metastasis. Compared with the low HIF1A-AS1 group, the high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines and was increased with the prolongation of nutrient-free culture. Inhibition of HIF1A-AS1 promoted starvation-induced HCC cell apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cell autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition. Conclusions: HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvationinduced HCC cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy, promoting HCC cell progression.

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RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-κB pathways

Cited by 42 publications

References 48 publications

Overexpression of RPN2 suppresses radiosensitivity of glioma cells by activating STAT3 signal transduction

Overexpression of RPN2 suppresses radiosensitivity of glioma cells by activating STAT3 signal transduction

JAK/STAT signaling in hepatocellular carcinoma

Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy

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