Different levels of let-7d expression modulate response of FaDu cells to irradiation and chemotherapeutics.

The implication of the let-7 family in cancer development is multifaceted. The family acts as tumor suppressor miRNA although overexpression of let-7 has also been described in many types of cancer, including head and neck squamous cell carcinoma (HNSCC). The aim of this study includes whether different expression levels of let-7d has an influence on chemo- and radiosensitivity. FaDu cell line models with a gradually increased level of let-7d (models from A to E) were generated with the lentiviral system. Expression levels of pluripotency, chemo-radioresistance/apoptosis, and targets of mRNAs were analyzed by real-time reverse transcription-PCR (qRT-PCR). Radiosensitivity was analyzed using a clonogenic assay after irradiation. Response to cisplatin, 5-FU, doxorubicin, and paclitaxel was done with MTT assay. Statistically significant decrease of K-RAS (p = 0.0369) and CASPASE3 (p = 0.0342) were observed with the growing expression level of let-7d. Cisplatin, 5-FU and doxorubicin caused similar decreased of cell survival with the increase of let-7d level (p = 0.004, post-trend p = 0.046; p = 0.004, post trend p = 0.0005 and p<0.0001, post trend p = 0.0001, respectively). All models were resistant to paclitaxel, irrespective of let-7d expression levels. Only two of the generated models (A and C) were radiosensitive (p = 0.0002). CONCLUSION: the above results indicated that the level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics.

The CDKN2a common variants: 148 Ala/Thr and 500 C/G in 3' UTR, and their association with clinical course of melanoma.

Changes in CDKN2a gene are known to be linked with sporadic melanoma and hereditary predisposition to this cancer. In the Polish population mutations in the coding region of the CDKN2a gene are rather rare, therefore the attention has been focused on polymorphisms and alterations in uncoding regions such as 3' UTR. The aim of this study was to analyze two common polymorphisms, Ala148Thr and 500 C/G, and correlate them with the clinical course of melanoma. DNA from 285 patients was analyzed and found polymorphisms were correlated with the clinical parameters employing statistical methods. The obtained results allow us to conclude: (i) survival times of 500 C/G carriers vs. cumulating proportion surviving was not statistically significant; (ii) CDKN2a polymorphism 500 C/G correlated with Ala148Thr; (iii) no correlation was observed between the 500 C/G polymorphism and age of diagnosis, localization of primary melanoma and survival time; (iv) we did not find correlation between 500 C/G and type of cancer in the family; (v) changes in the CDKN2a gene were not found in patients with second cancer.