Open AccessDifferent levels of let-7d expression modulate response of FaDu cells to irradiation and chemotherapeutics
Author(s) -
Katarzyna Lamperska,
Tomasz Kolenda,
Anna Teresiak,
Anna Kowalik,
Marta Kruszyna-Mochalska,
W. Jackowiak,
Renata Bliźniak,
Weronika Przybyła,
Marta Kapałczyńska,
Piotr Kozlowski
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0180265
Subject(s) - irradiation , chemistry , cancer research , microbiology and biotechnology , biology , physics , nuclear physics
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.