Τίτλος:
Contribution of miRNAs, tRNAs and TRFs to aberrant signaling and translation deregulation in lung cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Transcriptomics profiles of miRNAs, tRNAs or tRFs are used as biomarkers, after separate examination of several cancer cell lines, blood samples or biopsies. However, the possible contribution of all three profiles on oncogenic signaling and translation as a net regulatory effect, is under investigation. The present analysis of miRNAs and tRFs from lung cancer biopsies indicated putative targets, which belong to gene networks involved in cell proliferation, transcription and translation regulation. In addition, we observed differential expression of specific tRNAs along with several tRNA-related genes with possible involvement in carcinogenesis. Transfection of lung adenocarcinoma cells with two identified tRFs and subsequent NGS analysis indicated gene targets that mediate signaling and translation regulation. Broader analysis of all major signaling and translation factors in several biopsy specimens revealed a crosstalk between the PI3K/AKT and MAPK pathways and downstream activation of eIF4E and eEF2. Subsequent polysome profile analysis and 48S pre-initiation reconstitution experiments showed increased global translation rates and indicated that aberrant expression patterns of translation initiation factors could contribute to elevated protein synthesis. Overall, our results outline the modulatory effects that possibly correlate the expression of important regulatory non-coding RNAs with aberrant signaling and translation deregulation in lung cancer. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Skeparnias, I.
Anastasakis, D.
Grafanaki, K.
Kyriakopoulos, G.
Alexopoulos, P.
Dougenis, D.
Scorilas, A.
Kontos, C.
Stathopoulos, C.
Λέξεις-κλειδιά:
elongation factor; initiation factor 4E; microRNA; mitogen activated protein kinase; phosphatidylinositol 3 kinase; protein eEF2; protein kinase B; protein tRF; small untranslated RNA; transfer RNA; unclassified drug, Article; cell proliferation; controlled study; downstream processing; gene regulatory network; gene targeting; genetic transfection; high throughput sequencing; human; human cell; human tissue; lung adenocarcinoma; lung biopsy; lung cancer; lung carcinogenesis; MAPK signaling; Pi3K/Akt signaling; protein expression; protein protein interaction; RNA analysis; RNA transcription; signal transduction; transcriptomics; translation regulation; tumor-related gene
DOI:
10.3390/cancers12103056
