High expression of KLK5 enhances radiation resistance of cervical cancer
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ABSTRACT:
PROVIDER: PRJNA784279 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17055400_1.fastq.gz | Fastqsanger.gz | |||
| SRR17055400_2.fastq.gz | Fastqsanger.gz | |||
| SRR17055401_1.fastq.gz | Fastqsanger.gz | |||
| SRR17055401_2.fastq.gz | Fastqsanger.gz | |||
| SRR17055392_1.fastq.gz | Fastqsanger.gz |
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Project description:Studies have demonstrated the correlation between kallikrein-related peptidase 5 (KLK5) and cervical cancer prognosis, but studies on the correlation between KLK5 and radiation resistance are rare. Therefore, we aimed to investigate the role of high KLK5 expression in improving radiation resistance in cervical cancer and the underlying mechanisms. Samples from 29 patients with cervical cancer who received definitive radiotherapy without surgical treatment and other antineoplastic treatments (2014–2016) were analyzed. The patients were divided into the radiotherapy-sensitive (RS) group (18 patients without local recurrence and distant metastasis within 3 years after initial treatment) and the radiotherapy-resistant (RR) group (11 patients with uncontrolled conditions with radiotherapy, local recurrence, or distant metastasis within 3 years after initial treatment). We used high-throughput gene sequencing to detect radiosensitivity-related factors. We found that the expression of KLK5 in the RR group was higher than that in the RS group, and this result was associated with poor outcomes after radiotherapy as patients developed distant metastasis and showed recurrence at 2–3 years of follow-up. Besides, a high KLK5 expression enhances radiation resistance, indicating that, with further research, KLK5 may be used to develop novel molecular target-specific modulators for anti-cervical cancer therapy, acting as a prognostic agent in personalized precision medicine for cancer.
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Project description:The impact of obesity on radiation therapy outcome is unclear. Previously, we reported that obese patients with cervical cancer have superior outcomes following chemoradiation. We hypothesized that excess mono- and di- unsaturated fatty acids (uFFAs) enhance response to radiation. Here, using preclinical models, we show that uFFAs radiosensitize cervical cancer through a novel p53-dependent mechanism. UFFAs signaled through PPARgand p53 to promote lipid uptake, storage and metabolism after radiation. Stable isotope labeling confirmed that cervical cancer cells increase both catabolic and anabolic oleate metabolism in response to radiation, with associated increases in dependence on mitochondrial fatty acid oxidation for survival. In vivo, supplementation with exogenous oleate improved tumor growth delay in xenografts after radiation, an effect which could be partially mimicked in tumors from high fat diet induced obese mice. These results suggest that supplementation with uFFAs may improve tumor responses to radiation therapy, particularly in TP53 wild type tumors.
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Project description:We elucidated the potential role of STAT3 in the skin barrier and its effect on kallikrein-related peptidase 5 (KLK5) and serine protease inhibitor Kazal-type 5 (SPINK5) expression using a mouse model with keratinocyte-specific ablation of STAT3.
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Project description:Background. MicroRNAs (miRNAs) are short (~22 nt) non-coding regulatory RNAs that control gene expression at the translational level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. This prompted the development of miRNA-chips for cancer diagnosis or prognosis, opening a new door to understand carcinogenesis. Cervical cancer is one of the most common cancers in women worldwide. Therefore, there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform developed in house containing probes for mature miRNAs. Results. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL) and 9 low-grade squamous intraepithelial lesion (LSIL) samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, miRNAs deregulation in malignant and pre-malignant cervical tissues was detected after tackling the high variability observed. We were also able to identify putative targets of relevant candidate miRNAs. Conclusions. Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, deregulated miRNAs highlight new candidate targets allowing a better understanding of the molecular mechanism of this tumour type.
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Project description:It has been well-known that cancer cells acquire approximately three-fold radioresistance under hypoxia than under normoxia due to both radiation chemical and radiation biological mechanisms, causing a negative impact on the outcome of radiation therapy. In the present study, to identify genes responsive to hypoxia in human cervical epithelial adenocarcinoma HeLa cells, global-scale gene expression analysis was carried out using a GeneChip® system.
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Project description:Background. MicroRNAs (miRNAs) are short (~22 nt) non-coding regulatory RNAs that control gene expression at the translational level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. This prompted the development of miRNA-chips for cancer diagnosis or prognosis, opening a new door to understand carcinogenesis. Cervical cancer is one of the most common cancers in women worldwide. Therefore, there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform developed in house containing probes for mature miRNAs. Results. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL) and 9 low-grade squamous intraepithelial lesion (LSIL) samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, miRNAs deregulation in malignant and pre-malignant cervical tissues was detected after tackling the high variability observed. We were also able to identify putative targets of relevant candidate miRNAs. Conclusions. Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, deregulated miRNAs highlight new candidate targets allowing a better understanding of the molecular mechanism of this tumour type. In this study we used a common reference design experiment where the common reference used was a commercial RNA from normal cervix (Ambion) and the test samples were 4 pre-treatment squamous cell cervical carcinoma, 7 high-grade Squamous Intraepithelial Lesion (CINII, n=2 and CIN III, n=5) sample, 9 low-grade Squamous Intraepithelial Lesion (CIN I) samples, 19 normal cervix samples and 4 pools of normal cervix samples.
2010-08-01 | E-GEOD-19611 | biostudies-arrayexpress