Radiosensitivity of human ovarian cancer cells is enhanced by pseudolaric acid B due to the inhibition of the Ras/Raf/ERK signaling pathway

Song, Qingwei; Jiang, Sheng; Zhang, Xinxin; Pan, Ci; Chen, Lu; Peng, J; Li, Qingshui

doi:10.3892/etm.2017.5500

Cited by 5 publications

(6 citation statements)

References 26 publications

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“…We investigated significantly enriched KEGG pathways and the key target genes associated with these pathways. Our findings were in line with a range of previous studies, with respect to choline metabolism [27], the Ras-Raf-ERK signaling pathway [28], the estrogen receptor pathway [29], MAPK1 [30], PRKCB [31], PIK3CA [31], NRAS [32], PIK3R3 [33] and SOS1 [34]. These pathways have all been demonstrated to play vital roles in the aggressiveness, growth, and metastasis of OVC.…”

Section: Discussionsupporting

confidence: 92%

A risk score system based on a six-microRNA signature predicts the overall survival of patients with ovarian cancer

Zhou¹,

Wu²,

Yuan³

et al. 2022

J Ovarian Res

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Background Ovarian cancer (OVC) is a devastating disease worldwide; therefore the identification of prognostic biomarkers is urgently needed. We aimed to determine a robust microRNA signature-based risk score system that could predict the overall survival (OS) of patients with OVC. Methods We extracted the microRNA expression profiles and corresponding clinical data of 467 OVC patients from The Cancer Genome Atlas (TCGA) database and further divided this data into training, validation and complete cohorts. The key prognostic microRNAs for OVC were identified and evaluated by robust likelihood-based survival analysis (RLSA) and multivariable Cox regression. Time-dependent receiver operating characteristic (ROC) curves were then constructed to evaluate the prognostic performance of these microRNAs. A total of 172 ovarian cancer samples and 162 normal ovarian tissues were used to verify the credibility and accuracy of the selected markers of the TCGA cohort by quantitative real-time polymerase chain reaction (PCR). Results We successfully established a risk score system based on a six-microRNA signature (hsa-miR-3074-5p, hsa-miR-758-3p, hsa-miR-877-5p, hsa-miR-760, hsa-miR-342-5p, and hsa-miR-6509-5p). This microRNA based system is able to characterize patients as either high or low risk. The OS of OVC patients, with either high or low risk, was significantly different when compared in the training cohort (p < 0.001), the validation cohort (p < 0.001) and the complete cohort (p < 0.001). Analysis of clinical samples further demonstrated that these microRNAs were aberrantly expressed in OVC tissues. The six-miRNA-based signature was correlated with the prognosis of OVC patients (p < 0.001). Conclusions The study established a novel risk score system that is predictive of patient prognosis and is a potentially useful guide for the personalized treatment of OVC patients.

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Section: Discussionsupporting

confidence: 92%

A risk score system based on a six-microRNA signature predicts the overall survival of patients with ovarian cancer

Zhou¹,

Wu²,

Yuan³

et al. 2022

J Ovarian Res

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“…OC is a gynecological tumor with a high mortality rate, whose first-line therapy is combination of radiation treatment and chemotherapy [22]. However, drug resistance is one of the reasons that can lead to therapy failure.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated fibroblast-derived exosomal microRNA-98-5p promotes cisplatin resistance in ovarian cancer by targeting CDKN1A

Guo

Dong

et al. 2019

Cancer Cell Int

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BackgroundOvarian cancer (OC) is a gynecological malignancy with a high mortality. Cisplatin-based treatment is the typical treatment regimen for OC patients; however, it may cause unfavorable resistance. The current study intends to explore the function of cancer-associated fibroblast (CAF)-derived exosomal microRNA-98-5p (miR-98-5p) in cisplatin resistance in OC, and the participation of CDKN1A.MethodsBioinformatics analysis was employed in order to obtain cisplatin resistance-related differential genes in OC as well as possible upstream regulatory miRs. After gain- and loss-of-function assays in OC cells, RT-qPCR and western blot analysis were employed to measure CDKN1A and miR-98-5p expression. Dual luciferase reporter assay was applied to verify the targeting relationship between miR-98-5p and CDKN1A. CAFs were treated with miR-98-5p inhibitor, and then exosomes were isolated and co-cultured with OC cells. CCK-8, colony formation and flow cytometry assays were conducted to assess cell proliferation, cell colony formation, cell cycle distribution and cell apoptosis, respectively. At last, xenograft tumor in nude mice was carried out to test whether exosomal miR-98-5p could affect cisplatin resistance in OC in vivo.ResultsCDKN1A was highly expressed in cisplatin-sensitive OC cell lines, and silencing CDKN1A significantly promoted proliferation and cell cycle entry but decreased apoptosis in cisplatin-sensitive OC cells. miR-98-5p targeted CDKN1A to inhibit CDKN1A expression. CAF-derived exosomal miR-98-5p increased OC cell proliferation and cell cycle entry, but suppressed cell apoptosis. Furthermore, exosomal miR-98-5p promoted cisplatin resistance and downregulated CDKN1A in nude mice.ConclusionCollectively, CAF-derived exosomes carrying overexpressed miR-98-5p promote cisplatin resistance in OC by downregulating CDKN1A.

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“…The extracellular signal-regulated kinase (ERK) signaling pathway regulates cell proliferation, differentiation and survival, and mediates and amplifies signals during tumor invasion and metastasis (36). Previous studies have demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway is associated with tumor radiation resistance (37,38). In addition, previous studies have indicated that TRIM36 serves an inhibitory effect on the ERK signaling pathway in prostate cancer (39).…”

Section: Discussionmentioning

confidence: 99%

High expression of TRIM36 is associated with radiosensitivity in gastric cancer

et al. 2019

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Radiotherapy is one of the main adjuvant treatments for gastric cancer (GC) that can effectively reduce local recurrence and improve survival rates. However, radiotherapy may result in cytotoxicity and not benefit all patients. This highlights the requirement for identifying potential radiosensitivity genes in GC. The current study investigated the association between tripartite motif containing 36 (TRIM36) status and the prognosis of patients with GC receiving radiotherapy. A total of 371 patients with GC were selected from The Cancer Genome Atlas and randomly divided into test and the validation groups. The results revealed that TRIM36 expression was not associated with the overall survival (OS) rate. Patients who received radiotherapy with high TRIM36 expression had an improved OS rate compared with patients who did not receive radiotherapy in the test group, as demonstrated by univariate analysis [hazard ratio (HR), 0.062; 95% confidence interval (CI), 0.008–0.462; P=0.007] and multivariate analysis (HR, 0.095; 95% CI, 0.012–0.748; P=0.025). In the validation group, patients with high TRIM36 expression had decreased mortality risk when they received radiotherapy compared with patients who did not receive radiotherapy, as determined by univariate analysis (HR, 0.190; 95% CI, 0.067–0.540; P=0.002) and multivariate analysis (HR, 0.075; 95% CI, 0.020–0.276; P<0.001). However, for patients with low expression, no significant difference was identified in the overall survival rates between the radiotherapy and non-radiotherapy groups. Chi-squared analysis revealed that the expression status of TRIM36 was an independent factor and was not associated with clinicopathological factors. The results indicated that patients with high TRIM36 expression receiving radiotherapy exhibited an improved OS rate. TRIM36 may therefore be an important factor affecting the clinical prognosis of patients with GC receiving radiotherapy and may be considered as a potential radiosensitivity gene signature.

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Radiosensitivity of human ovarian cancer cells is enhanced by pseudolaric acid B due to the inhibition of the Ras/Raf/ERK signaling pathway

Cited by 5 publications

References 26 publications

A risk score system based on a six-microRNA signature predicts the overall survival of patients with ovarian cancer

A risk score system based on a six-microRNA signature predicts the overall survival of patients with ovarian cancer

Cancer-associated fibroblast-derived exosomal microRNA-98-5p promotes cisplatin resistance in ovarian cancer by targeting CDKN1A

High expression of TRIM36 is associated with radiosensitivity in gastric cancer

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