TNPO2 operates downstream of DYNC1I1 and promotes gastric cancer cell proliferation and inhibits apoptosis

Gong, Libao; Wen, Ti; Li, Zhi; Wang, Yizhe; Wang, Jin; Che, Xiaofang; Liu, Yunpeng; Qu, Xiujuan

doi:10.1002/cam4.2582

Cited by 10 publications

(11 citation statements)

References 40 publications

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“…Previous studies confirmed that the lack of DYNC1I1 could lead to the occurrence of neuronal autophagy, which was highly correlated to diseases such as aging and neuronal atrophy [28] . In addition, some studies have reported that the upregulation of DYNC1I1 could inhibit the apoptosis of cancer cells and promote the proliferation and migration of cancer cells [29]. DYNC1I1, the binding subunit of cytoplasmic dynein, could assist the cytoplasmic dynein-mediated transport of P65 to the nucleus, following which P65 could promote the expression of IL-6 and activate the STAT3 phosphorylation to promote the proliferation and metastasis of gastric cancer cells [30].…”

Section: Discussionmentioning

confidence: 99%

“…DYNC1I1, the binding subunit of cytoplasmic dynein, could assist the cytoplasmic dynein-mediated transport of P65 to the nucleus, following which P65 could promote the expression of IL-6 and activate the STAT3 phosphorylation to promote the proliferation and metastasis of gastric cancer cells [30]. Moreover, DYNC1I1 upregulation could also enhance its downstream TNPO2 expression through SP1 overexpression to promote the proliferation and invasion of gastric cancer cells [29]. This study remarkably found that circCCNB1 silencing induced GPM6A under-expression and DYNC1I1 overexpression to promote the proliferation and invasion of HCC cells by activating the AKT/ERK signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

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CircCCNB1 silencing acting as a miR-106b-5p sponge inhibited GPM6A expression to promote HCC progression by enhancing DYNC1I1 expression and activating the AKT/ERK signaling pathway

Liu¹,

Cao²,

Zhao³

et al. 2022

Int. J. Biol. Sci.

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Background: Circular RNAs (circRNAs), which generally act as microRNA (miRNA) sponges to competitively regulate the downstream target genes of miRNA, play an essential role in cancer biology. However, few studies have been reported on the role of circRNA based competitive endogenous RNA (ceRNA) network in hepatocellular carcinoma (HCC). Herein, we aimed to screen and establish the circRNA/miRNA/mRNA networks related to the prognosis and progression of HCC and further explore the underlying mechanisms of tumorigenesis. Methods: GEO datasets GSE97332, GSE108724, and GSE101728 were utilized to screen the differentially expressed circRNAs (DE-circRNAs), DE-miRNAs, and DEmRNAs between HCC and matched para-carcinoma tissues. After six RNA-RNA predictions and five intersections between DE-RNAs and predicted RNAs, the survival-related RNAs were screened by the ENCORI analysis tool. The ceRNA networks were constructed using Cytoscape software, based on two models of up-regulated circRNA/down-regulated miRNA/up-regulated mRNA and down-regulated circRNA/up-regulated miRNA/down-regulated mRNA. The qRT-PCR assay was utilized for detecting the RNA expression levels in HCC cells and tissues. The apoptosis, Edu, wound healing, and transwell assays were performed to evaluate the effect of miR-106b-5p productions on the proliferation, invasion, and metastasis of HCC cells. In addition, the clone formation, cell cycle, and nude mice xenograft tumor assays were used to investigate the influence of hsa_circ_0001495 (circCCNB1) silencing and overexpression on the proliferation of HCC cells in vitro and in vivo. Furthermore, the mechanism of downstream gene DYNC1I1 and AKT/ERK signaling pathway via the circCCNB1/miR-106b-5p/GPM6A network in regulating the cell cycle was also explored. Results: Twenty DE-circRNAs with a genomic length less than 2000bp, 11 survival-related DE-miRNAs, and 61 survival-related DE-mRNAs were screened out and used to construct five HCC related ceRNA networks. Then, the circCCNB1/miR-106b-5p/GPM6A network was randomly selected for subsequent experimental verification and mechanism exploration at in vitro and in vivo levels. The expression of circCCNB1 and GPM6A were significantly down-regulated in HCC cells and cancer tissues, while miR-106b-5p expression was up-regulated. After transfections, miR-106b-5p mimics notably enhanced the proliferation, invasion, and metastasis of HCC cells, while the opposite was seen with miR-105b-5p inhibitor. In addition, circCCNB1 silencing promoted the clone formation ability, the cell cycle G1-S transition, and the growth of xenograft tumors of HCC cells via GPM6A downregulation. Subsequently, under-expression of GPM6A increased DYNC1I1 expression and activated the phosphorylation of the AKT/ERK pathway to regulate the HCC cell cycle. Ivyspring International PublisherConclusions: We demonstrated that circCCNB1 silencing promoted cell proliferation and metastasis of HCC cells by weakening sponging of oncogenic miR-106b-5p to induce GPM6A underexpression. DYNC1I1 gene expressio...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CircCCNB1 silencing acting as a miR-106b-5p sponge inhibited GPM6A expression to promote HCC progression by enhancing DYNC1I1 expression and activating the AKT/ERK signaling pathway

Liu¹,

Cao²,

Zhao³

et al. 2022

Int. J. Biol. Sci.

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“…Pilot studies have noted DYNC1I1 (dynein cytoplasmic 1 intermediate chain 1) was an adverse factor for the prognosis of patients with liver hepatocellular carcinoma, gastric cancer, colon cancer and glioblastoma ( Gong L.-B. et al, 2019 ; Gong L. et al, 2019 ; Sakthikumar et al, 2020 ; Yin et al, 2020 ; Zhou J. et al, 2021 ). There were no published researches on the ADPRHL1, DYNC1I1, KCNG1 in HNSCC before to our knowledge.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Prognostic Model Based on Fatty Acid Metabolism-Related Genes of Head and Neck Squamous Cell Carcinoma

Chai

Zong

et al. 2022

Front. Genet.

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The fatty acid metabolism (FAM) is known to impact tumorigenesis, tumor progression and treatment resistance via enhancing lipid synthesis, storage and catabolism. However, the role of FAM in head and neck squamous cell carcinoma (HNSCC) has remained elusive. In the present study, we obtained a total of 69 differentially expressed FAM-related genes between 502 HNSCC samples and 44 normal samples from The Cancer Genome Atlas (TCGA) database. The HNSCC samples were divided into 2 clusters according to 69 differentially expressed genes (DEGs) via cluster analysis. Then DEGs in the two clusters were found, and 137 prognostic DEGs were identified by univariate analysis. Subsequently, combined with the clinical information of 546 HNSCC patients from TCGA database, a 12-gene prognostic risk model was established (FEPHX3, SPINK7, FCRLA, MASP1, ZNF541, CD5, BEST2 and ZAP70 were down-regulation, ADPRHL1, DYNC1I1, KCNG1 and LINC00460 were up-regulation) using multivariate Cox regression and LASSO regression analysis. The risk scores of 546 HNSCC samples were calculated. According to the median risk score, 546 HNSCC patients were divided into the high- and low-risk (high- and low score) groups. The Kaplan-Meier survival analysis showed that the survival time of HNSCC patients was significantly shorter in the high-risk group than that in the low-risk group (p < 0.001). The same conclusion was obtained in the Gene Expression Omnibus (GEO) dataset. After that, the multivariate Cox regression analysis indicated that the risk score was an independent factor for patients with HNSCC in the TCGA cohort. In addition, single-sample gene set enrichment analysis (ssGSEA) indicated that the level of infiltrating immune cells was relatively low in the high-risk group compared with the low-risk group. In summary, FAM-related gene expression-based risk signature could predict the prognosis of HNSCC independently.

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“…SiRNA knockdown reduced tumour cell proliferation, colony formation and migration abilities and increased apoptosis in vitro. 26,27 Karyopherin-α1 (KPNA1) expression is elevated in colon cancer and tracks with disease progression. Colon cancer cell proliferation, migration, colony formation and in vivo xenograft tumour growth was impaired by KPNA1 genetic knockout and enhanced by overexpression of the import protein.…”

Section: Other Nuclear Transport Receptors In Cancermentioning

confidence: 99%

Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy

Newell,

van der Watt,

Leaner

2023

IUBMB Life

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Systemic modalities are crucial in the management of disseminated malignancies and liquid tumours. However, patient responses and tolerability to treatment are generally poor and those that enter remission often return with refractory disease. Combination therapies provide a methodology to overcome chemoresistance mechanisms and address dose‐limiting toxicities. A deeper understanding of tumorigenic processes at the molecular level has brought a targeted therapy approach to the forefront of cancer research, and novel cancer biomarkers are being identified at a rapid rate, with some showing potential therapeutic benefits. The Karyopherin superfamily of proteins is soluble receptors that mediate nucleocytoplasmic shuttling of proteins and RNAs, and recently, nuclear transport receptors have been recognized as novel anticancer targets. Inhibitors against nuclear export have been approved for clinical use against certain cancer types, whereas inhibitors against nuclear import are in preclinical stages of investigation. Mechanistically, targeting nucleocytoplasmic shuttling has shown to abrogate oncogenic signalling and restore tumour suppressor functions through nuclear sequestration of relevant proteins and mRNAs. Hence, nuclear transport inhibitors display broad spectrum anticancer activity and harbour potential to engage in synergistic interactions with a wide array of cytotoxic agents and other targeted agents. This review is focussed on the most researched nuclear transport receptors in the context of cancer, XPO1 and KPNB1, and highlights how inhibitors targeting these receptors can enhance the therapeutic efficacy of standard of care therapies and novel targeted agents in a combination therapy approach. Furthermore, an updated review on the therapeutic targeting of lesser characterized karyopherin proteins is provided and resistance to clinically approved nuclear export inhibitors is discussed.

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TNPO2 operates downstream of DYNC1I1 and promotes gastric cancer cell proliferation and inhibits apoptosis

Cited by 10 publications

References 40 publications

CircCCNB1 silencing acting as a miR-106b-5p sponge inhibited GPM6A expression to promote HCC progression by enhancing DYNC1I1 expression and activating the AKT/ERK signaling pathway

CircCCNB1 silencing acting as a miR-106b-5p sponge inhibited GPM6A expression to promote HCC progression by enhancing DYNC1I1 expression and activating the AKT/ERK signaling pathway

Identification of a Prognostic Model Based on Fatty Acid Metabolism-Related Genes of Head and Neck Squamous Cell Carcinoma

Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy

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