MiR-205 and miR-218 expression is associated with carboplatin chemoresistance and regulation of apoptosis via Mcl-1 and Survivin in lung cancer cells.
Lung cancer chemoresistance is the most frequent barrier in lung cancer therapy. Recent studies have indicated that microRNAs play a significant role in this mechanism and can function as either tumor suppressor or tumor promoters. However the effect of miRNA in lung cancer chemoresistance is poorly understood. Therefore, in the present study we investigated the role of two distinct miR members, the miR-205 and the tumor suppressor miR-218 in the proliferation, invasion and induction of apoptosis in lung cancer cells after carboplatin treatment. The results showed that miR-205 overexpression in A549 and H1975 lung cancer cells is concurrent with the down regulation of miR-218 and in linked with carboplatin sensitivity and chemoresistance. Interestingly, ectopic miR-218 overexpression reduced cell proliferation, invasion and migration of lung cancer cells, whereas miR-205 rescued the suppressive effect of miR-218 by altering the expression levels of the pro-apoptotic proteins PARP, Caspase 3, Bax and upregulating the anti-apoptotic markers Mcl-1 and Survivin. Taken together our findings imply that the miRNAs miR-205 and miR-218 play a key role in the development of lung cancer acquired chemoresistance and the tumor suppressor role of miR-218 in inhibiting lung cancer cell tumorigenesis and overcoming platinum chemoresistance is significant for future cancer therapeutic approaches.
Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece.
Paul
P
Zarogoulidis
Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: spetanid@auth.gr.
Savvas
S
Petanidis
Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Efrosini
E
Kioseoglou
Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece.
Kalliopi
K
Domvri
Department of Medicine, Laboratory of General Biology, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece; Department of Medicine, Laboratory of Forensic Medicine and Toxicology, Aristotle University of Thessaloniki, 54124, Greece.
Doxakis
D
Anestakis
Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece.
Konstantinos
K
Zarogoulidis
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016190:Carboplatin / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D013997:Time Factors; D046509:Tissue Culture Techniques; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D016190:Carboplatin; D053148:Caspase 3; D051034:Inhibitor of Apoptosis Proteins; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011065:Poly(ADP-ribose) Polymerases; D000077022:Survivin; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C107489:BIRC5 protein, human; C579095:MCL1 protein, human; C534425:MIR205, human; C547471:MIRN218 microRNA, human; C505407:CASP3 protein, human
Apoptosis; Carboplatin chemoresistance; Lung cancer; MiR-218; Survivin