Let-7b attenuates cisplatin resistance and tumor growth in gastric cancer by targeting AURKB

Han, Xiao; Zhang, Jingjing; Zhao, Han; Zhang, Haibin; Wang, Zi-An

doi:10.1038/s41417-018-0048-8

Cited by 41 publications

(26 citation statements)

References 31 publications

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“…To explore the specific mechanism of MAPRE2 regulating cisplatin drug sensitivity, we use the public database https://string-db.org/ to explore MAPRE2 ′ interaction protein (Supplementary Figure 3A) and search their expression level and change through our protein chip (Supplementary Figure 3B). Among them, AURKB is significantly high expression in A549/DDP, and it has been confirmed that its high expression is related to cisplatin resistance (40,41). Then, DNA damage repair gene set was obtained from GSEA, and the correlation between MAPRE2 and the DNA damage repair gene was analyzed by String.…”

Section: Figure 6 |mentioning

confidence: 99%

WDHD1 Leads to Cisplatin Resistance by Promoting MAPRE2 Ubiquitination in Lung Adenocarcinoma

Gong

Xiao

et al. 2020

Front. Oncol.

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Ubiquitin ligases have been shown to regulate drug sensitivity. This study aimed to explore the role of the ubiquitin ligase WD repeat and HMG-box DNA binding protein 1 (WDHD1) in regulating cisplatin sensitivity in lung adenocarcinoma (LUAD). A quantitative analysis of the global proteome identified differential protein expression between LUAD A549 cells and the cisplatin-resistant strain A549/DDP. Public databases revealed the relationship between ubiquitin ligase expression and the prognosis of patients with LUAD. Quantitative real-time polymerase chain reaction and Western blotting were used to estimate the WDHD1 expression levels. Analysis of public databases predicted the substrate of WDHD1. Western blotting detected the effect of WDHD1 on microtubule-associated protein RP/EB family member 2 (MAPRE2) and DSTN. Functional analysis of MAPRE2 verified the interaction between WDHD1 and MAPRE2, as well as the interacting sites by methyl-thiazolyl-tetrazolium assay and flow cytometry, immunoprecipitation, protein stability, and immunofluorescence. Cell and animal experiments confirmed the effect of WDHD1 and MAPRE2 on cisplatin sensitivity in LUAD. Clinical data evaluated the impact of WDHD1 expression level on cisplatin sensitivity. Quantitative analysis of the global proteome revealed ubiquitin-dependent protein catabolism to be more active in A549/DDP cells than in A549 cells. WDHD1 expression was higher in A549/DDP cells than in A549 cells, and knocking out WDHD1 increased the sensitivity of A549/DDP cells to cisplatin. WDHD1 overexpression negatively correlated with the overall survival of LUAD patients. We observed that MAPRE2 was upregulated when WDHD1 was knocked out. A MAPRE2 knockout in A549 cells resulted in increased cell viability while decreasing apoptosis when the A549 cells exposed to cisplatin. WDHD1 and MAPRE2 were found to interact in the nucleus, and WDHD1 promoted the ubiquitination of MAPRE2. Following cisplatin exposure, the WDHD1 and MAPRE2 knockout groups facilitated cell proliferation and migration, inhibited apoptosis in A549/DDP cells, decreased apoptosis, and increased tumor size and growth rate in animal experiments. Gong et al. Chemotherapy Resistance of Lung Adenocarcinoma Immunohistochemistry showed that Ki67 levels increased, and levels of apoptotic indicators significantly decreased in the WDHD1 and MAPRE2 knockout groups. Clinical data confirmed that WDHD1 overexpression negatively correlated with cisplatin sensitivity. Thus, the ubiquitin ligase WDHD1 induces cisplatin resistance in LUAD by promoting MAPRE2 ubiquitination.

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Section: Figure 6 |mentioning

confidence: 99%

WDHD1 Leads to Cisplatin Resistance by Promoting MAPRE2 Ubiquitination in Lung Adenocarcinoma

Gong

Xiao

et al. 2020

Front. Oncol.

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“…Some researchers found that high expression of AURKB was associated with the improved overall survival in GC, 12 however, others considered that inhibition of AURKB reduced GC cell viability and increased the sensitivity of resistant GC cell to cisplatin. 13 , 14 Hence, the exact effect of AURKB in GC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

<p><em>AURKB</em> Promotes the Metastasis of Gastric Cancer, Possibly by Inducing EMT</p>

Wang¹,

Zhu²,

Wang³

et al. 2020

CMAR

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Aim To investigate the function of Aurora kinase B (AURKB) in gastric cancer (GC). Methods Immunohistochemistry was used to assay the expression of AURKB in 50 pairs of GC and adjacent tissues, and qRT-PCR was conducted to test AURKB expression in normal gastric epithelial and GC cell lines. Two segments of small interference RNAs (siRNAs) targeting AURKB were synthesized and inserted into GV248 lentivirus vector. After transfected with LV-AURKB-RNAis, CCK8, wound healing, transwell and flow cytometric assays were performed to determine the influence of silencing AURKB on cell proliferation, invasion, migration, cell cycles and apoptosis of GC cells, and the expression of EMT (epithelial–mesenchymal transition)-related markers was demonstrated by Western blots (WB). Results AURKB was highly expressed in GC and closely associated with lymph node metastasis and advanced stages of GC. Down-regulating AURKB suppressed the proliferation and promoted the apoptosis of GC cells, arrested the cell cycle in G2/M phase, and inhibited the invasion and migration of GC cells. The expression levels of AKT1, mTOR, Myc, MMP2, and VEGFA were decreased, while the expression levels of OCLN and JUP were increased after knocking down of AURKB in both AGC and MKN45 cells. Conclusion AURKB is overexpressed in GC and closely associated with clinicopathologic characteristics of GC. It is likely that by inhibiting VEGFA/Akt/mTOR and Wnt/β-catenin/Myc pathways, silenced AURKB could inhibit the invasive and migratory abilities of GC cells. However, because of the small sample size and the absence of in-vivo experiments, these results should be verified by further studies.

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“…Similarly, tumor suppressor miR-362-5p, miR-198, miR-574-3p, miR-876-3p, miR-874 and let-7b have been reported to reverse DDP resistance of gastric cancer cells via silencing suppressor of zeste 12 protein (SUZ12), fibroblast growth factor receptor 1 (FGFR1), zinc finger E-box binding homeobox transcription factor 1 (ZEB1), TMED3, autophagy-related 16-like 1 (ATG16 L1) and AURKB, respectively [117][118][119][120][121][122]. In addition, via targeting excision repair cross-complementing (ERCC), exogenous over-expression of tumor suppressor miR-122, miR-138-5p and miR-192-5p could also reverse DDP resistance of gastric cancer [48,123,124].…”

Section: Mirnas and Resistance To Platinum Drugsmentioning

confidence: 99%

Noncoding RNAs in gastric cancer: implications for drug resistance

et al. 2020

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Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.

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Let-7b attenuates cisplatin resistance and tumor growth in gastric cancer by targeting AURKB

Cited by 41 publications

References 31 publications

WDHD1 Leads to Cisplatin Resistance by Promoting MAPRE2 Ubiquitination in Lung Adenocarcinoma

WDHD1 Leads to Cisplatin Resistance by Promoting MAPRE2 Ubiquitination in Lung Adenocarcinoma

<p><em>AURKB</em> Promotes the Metastasis of Gastric Cancer, Possibly by Inducing EMT</p>

Noncoding RNAs in gastric cancer: implications for drug resistance

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