scholarly journals MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinhong Ge ◽  
Suryakant Niture ◽  
Minghui Lin ◽  
Patrice Cagle ◽  
P. Andy Li ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cell Carcinoma ◽  
Kinase Inhibitor ◽  
Ectopic Expression ◽  
Cancer Cell Proliferation ◽  
Growth And Survival ◽  
Cellular Autophagy ◽  
Increased Sensitivity ◽  
Factor Α

AbstractTumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of the TIPE/TNFAIP8 family which regulates tumor growth and survival. Our goal is to delineate the detailed oncogenic role of TNFAIP8 in skin cancer development and progression. Here we demonstrated that higher expression of TNFAIP8 is associated with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma development in patient tissues. Induction of TNFAIP8 expression by TNFα or by ectopic expression of TNFAIP8 in SCC or melanoma cell lines resulted in increased cell growth/proliferation. Conversely, silencing of TNFAIP8 decreased cell survival/cell migration in skin cancer cells. We also showed that miR-205-5p targets the 3′UTR of TNFAIP8 and inhibits TNFAIP8 expression. Moreover, miR-205-5p downregulates TNFAIP8 mediated cellular autophagy, increased sensitivity towards the B-RAFV600E mutant kinase inhibitor vemurafenib, and induced cell apoptosis in melanoma cells. Collectively our data indicate that miR-205-5p acts as a tumor suppressor in skin cancer by targeting TNFAIP8.

The patient with renal cell cancer

2015 ◽  
Author(s):  
Tim Eisen
Keyword(s):  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cancer ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Cell Cancer

Renal cancer is the commonest malignancy of the kidney and worldwide, accounts for between 2% and 3% of the total cancer burden. The mainstay of curative treatment remains surgery. There have been significant advances in surgical technique, the most important ones being nephron-sparing surgery and laparoscopic nephrectomy. The medical treatment of advanced renal cell cancer has only improved markedly in the last decade with the development of antiangiogenic tyrosine-kinase inhibitors, inhibitors of mammalian target of rapamycin, and a diminished role for immunotherapy.Tyrosine-kinase inhibitor therapy results in reduction of tumour volume in around three-quarters of patients and doubles progression-free survival, but treatment is not curative. The management of side effects in patients on maintenance tyrosine-kinase inhibitors has improved in the last 3 years, although still presents difficulties which have to be actively considered.The molecular biology of renal cell carcinoma is better understood than for the majority of solid tumours. The commonest form of renal cancer, clear-cell carcinoma of the kidney, is strongly associated with mutations in the von Hippel–Lindau gene and more recently with chromatin-remodelling genes such as PBRM1. These genetic abnormalities lead to a loss of control of angiogenesis and uncontrolled proliferation of tumour cells. There is a very wide spectrum of tumour behaviour from the extremely indolent to the terribly aggressive. It is not currently known what accounts for this disparity in tumour behaviour.A number of outstanding questions are being addressed in scientific and clinical studies such as a clearer understanding of prognostic and predictive molecular biomarkers, the role of adjuvant therapy, the role of surgery in the presence of metastatic disease, how best to use our existing agents, and investigation of novel targets and therapeutic agents, especially novel immunotherapies.

scholarly journals Nipped-B-like Protein Sensitizes Esophageal Squamous Cell Carcinoma Cells to Cisplatin via Upregulation of PUMA

2020 ◽  
Vol 19 ◽  
pp. 153303382096072
Author(s):  
Shengjie Zhang ◽  
Yun Zhou ◽  
Qinchuan Wang ◽  
Kristine Donahue ◽  
Jianguo Feng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Ectopic Expression ◽  
Carcinoma Cells ◽  
Downstream Effector ◽  
Endogenous Expression ◽  
Cisplatin Sensitivity ◽  
Increased Sensitivity

Nipped-B-like protein plays a pivotal role as a cohesin loading factor in the segregation of chromosomes when cells divide. Accumulating evidence indicates that alterations of this protein are involved in human carcinogenesis, especially in the regulation of chemotherapeutic drug response. However, the role of Nipped-B-like protein in esophageal squamous cell carcinoma remains unknown. In this study, we investigated the relevance of Nipped-B-like protein in the regulation of cisplatin sensitivity in esophageal squamous cell carcinoma. Ectopic expression of Nipped-B-like protein inhibited the growth of COLO-680N cells with low endogenous expression levels of Nipped-B-like protein, and increased sensitivity to cisplatin, a commonly used chemotherapy drug for patients with esophageal squamous cell carcinoma. In contrast, loss of Nipped-B-like protein stimulated the growth of EC9706 and Eca-109 cells with high levels of the protein, and resulted in resistance to cisplatin. P53-upregulated modulator of apoptosis, which is essential in the modulation of cisplatin sensitivity in a variety of cancers, acts as a downstream effector of Nipped-B-like protein. Restoration of this pro-apoptotic protein in Nipped-B-like protein-overexpressing esophageal squamous cell carcinoma cells effectively increased cisplatin sensitivity. Conversely, the silencing of P53-upregulated modulator of apoptosis in Nipped-B-like protein-depleted esophageal squamous cell carcinoma rendered cells resistant to cisplatin. Moreover, Nipped-B-like protein could bind directly to the promoter region of P53-upregulated modulator of apoptosis. In summary, our study addresses the involvement of Nipped-B-like protein in the development of esophageal squamous cell carcinoma, and the modulation of cisplatin sensitivity via regulation of P53-upregulated modulator of apoptosis.

Geographic Pathology of Skin Cancer

1999 ◽  
Vol 3 (3) ◽  
pp. 120-122
Author(s):  
Robert Jackson
Keyword(s):  
Squamous Cell Carcinoma ◽  
Skin Cancer ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Basal Cell ◽  
Sun Exposure

Background: The development of knowledge concerning the role of sun exposure in causing skin cancer has been a gradual one. Objective: This article reviews the article by Urbach who used manikin coated with an ultraviolet dosimeter to see exactly where on the head and neck the exposure was greatest. Conclusion: Urbach showed that the areas of greatest sun exposure on his manikins corresponded with the location of 95% of squamous cell carcinoma and 66% of basal cell carcinoma. He also clearly showed the importance of scattered sky and reflected radiation.

scholarly journals PATZ1 (MAZR) Co-occupies Genomic Sites With p53 and Inhibits Liver Cancer Cell Proliferation via Regulating p27

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhen Long Ng ◽  
Jiamin Siew ◽  
Jia Li ◽  
Guanxu Ji ◽  
Min Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cellular Proliferation ◽  
Zinc Finger Protein ◽  
Kinase Inhibitor ◽  
Transcriptional Start Site ◽  
Cancer Cell Proliferation

Liver cancer is the third most common cause of cancer death in the world. POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1/MAZR) is a transcription factor associated with various cancers. However, the role of PATZ1 in cancer progression remains controversial largely due to lack of genome-wide studies. Here we report that PATZ1 regulates cell proliferation by directly regulating CDKN1B (p27) in hepatocellular carcinoma cells. Our PATZ1 ChIP-seq and gene expression microarray analyses revealed that PATZ1 is strongly related to cancer signatures and cellular proliferation. We further discovered that PATZ1 depletion led to an increased rate of colony formation, elevated Ki-67 expression and greater S phase entry. Importantly, the increased cancer cell proliferation was accompanied with suppressed expression of the cyclin-dependent kinase inhibitor CDKN1B. Consistently, we found that PATZ1 binds to the genomic loci flanking the transcriptional start site of CDKN1B and positively regulates its transcription. Notably, we demonstrated that PATZ1 is a p53 partner and p53 is essential for CDKN1B regulation. In conclusion, our study provides novel mechanistic insights into the inhibitory role of PATZ1 in liver cancer progression, thereby yielding a promising therapeutic intervention to alleviate tumor burden.

Targeting of the N-terminal coiled coil oligomerization interface of BCR interferes with the transformation potential of BCR-ABL and increases sensitivity to STI571

Blood ◽  
2003 ◽  
Vol 102 (8) ◽  
pp. 2985-2993 ◽  
Author(s):  
Tim Beissert ◽  
Elena Puccetti ◽  
Andrea Bianchini ◽  
Saskia Güller ◽  
Simone Boehrer ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Coiled Coil ◽  
Chromosome 9 ◽  
Abl Kinase ◽  
Kinase C ◽  
Coiled Coil Region ◽  
Increased Sensitivity ◽  
Transformation Potential

Abstract Translocations involving the abl locus on chromosome 9 fuses the tyrosine kinase c-ABL to proteins harboring oligomerization interfaces such as BCR or TEL, enabling these ABL-fusion proteins (X-ABL) to transform cells and to induce leukemia. The ABL kinase activity is blocked by the ABL kinase inhibitor STI571 which abrogates transformation by X-ABL. To investigate the role of oligomerization for the transformation potential of X-ABL and for the sensitivity to STI571, we constructed ABL chimeras with oligomerization interfaces of proteins involved in leukemia-associated translocations such as BCR, TEL, PML, and PLZF. We assessed the capacity of these chimeras to form high molecular weight (HMW) complexes as compared with p185(BCR-ABL). There was a direct relationship between the size of HMW complexes formed by these chimeras and their capacity to induce factor independence in Ba/F3 cells, whereas there was an inverse relationship between the size of the HMW complexes and the sensitivity to STI571. The targeting of the oligomerization interface of p185(BCR-ABL) by a peptide representing the coiled coil region of BCR reduced its potential to transform fibroblasts and increased sensitivity to STI571. Our results indicate that targeting of the oligomerization interfaces of the X-ABL enhances the effects of STI571 in the treatment of leukemia caused by X-ABL.

scholarly journals The Role of p53 in Progression of Cutaneous Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4507
Author(s):  
Minna Piipponen ◽  
Pilvi Riihilä ◽  
Liisa Nissinen ◽  
Veli-Matti Kähäri
Keyword(s):  
Squamous Cell Carcinoma ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tp53 Gene ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Epidermal Keratinocytes ◽  
Early Event ◽  
Skin Cancers

Skin cancers are the most common types of cancer worldwide, and their incidence is increasing. Melanoma, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the three major types of skin cancer. Melanoma originates from melanocytes, whereas BCC and cSCC originate from epidermal keratinocytes and are therefore called keratinocyte carcinomas. Chronic exposure to ultraviolet radiation (UVR) is a common risk factor for skin cancers, but they differ with respect to oncogenic mutational profiles and alterations in cellular signaling pathways. cSCC is the most common metastatic skin cancer, and it is associated with poor prognosis in the advanced stage. An important early event in cSCC development is mutation of the TP53 gene and inactivation of the tumor suppressor function of the tumor protein 53 gene (TP53) in epidermal keratinocytes, which then leads to accumulation of additional oncogenic mutations. Additional genomic and proteomic alterations are required for the progression of premalignant lesion, actinic keratosis, to invasive and metastatic cSCC. Recently, the role of p53 in the invasion of cSCC has also been elucidated. In this review, the role of p53 in the progression of cSCC and as potential new therapeutic target for cSCC will be discussed.

Prognostic Factors and the Role of Adjuvant Radiation Therapy in Non-Melanoma Skin Cancer of the Head and Neck

2015 ◽  
pp. e513-e518 ◽  
Author(s):  
Sandro V. Porceddu
Keyword(s):  
Radiation Therapy ◽  
Prognostic Factors ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Adjuvant Radiation ◽  
Adjuvant Radiation Therapy ◽  
Non Melanoma Skin Cancer ◽  
Melanoma Skin

Non-melanoma skin cancer (NMSC) is the most common cancer worldwide. Among the two types of NMSC, basal cell carcinoma (BCC) accounts for approximately 75% to 80% of cases and cutaneous squamous cell carcinoma (cSCC) accounts for 20% to 25% of cases. The majority of lesions are low risk and treated with simple surgical excision, which provides histopathologic information and is associated with high cure rates and acceptable cosmetic and functional outcomes. cSCCs are generally more aggressive than BCCs. NMSC commonly occurs in the sun-exposed head and neck region (80% to 90%). Approximately 5% of patients with NMSC (mainly cSCC) will have clinicopathologic features that predict for an increased risk for local and regional recurrence and, rarely, distant relapse. These features include locally advanced primary disease (stage T3-T4), regional nodal involvement, clinical perineural invasion, recurrent disease following treatment, and immunosuppression. Patients who have these features may warrant review by a multidisciplinary tumor board and might require combined modality treatment involving surgery and adjuvant radiation therapy (RT). This article focuses on our current understanding of the prognostic factors and role of adjuvant RT in high-risk NMSC of the head and neck.

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