Mitochondrial Elongation and OPA1 Play Crucial Roles during the Stemness Acquisition Process in Pancreatic Ductal Adenocarcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. RNA Extraction and Real-Time PCR (qPCR)
2.3. mtDNA Quantification
Gene | Primer Pairs–Sequence (5′-3′) | |
---|---|---|
Forward | Reverse | |
NRF1 | CCACGTTACAGGGAGGTGAG | TGTAGCTCCCTGCTGCATCT |
NRF2 | GCGACGGAAAGAGTATGAGC | GTTGGCAGATCCACTGGTTT |
TFAM | GTGGTTTTCATCTGTCTTGGC | ACTCCGCCCTATAAGCATCTTG |
PGC1α | TGACTGGCGTCATTCAGGAG | CCAGAGCAGCACACTCGAT |
CDH1 | GACACCAACGATAATCCTCCGA | GGCACCTGACCCTTGTACGT |
ZEB1 | GTTACCAGGGAGGAGCAGTGAAA | GACAGCAGTGTCTTGTTGTTGTAGAAA |
SOX2 | GGGAAATGGGAGGGGTGCAAAAGAGG | TTGCGTGAGTGTGGATGGGATTGGTG |
NANOG | AGTCCCAAAGGCAAACAACCCACTTC | TGCTGGAGGCTGAGGTATTTCTGTCTC |
OCT3/4 | GACAGGGGGAGGGGAGGAGCTAGG | CTTCCCTCCAACCAGTTGCCCCAAAC |
ND1 * | GTCAACCTCGCTTCCCCACCCT | TCCTGCGAATAGGCTTCCGGCT |
B2M * | CGACGGGAGGGTCGGGACAA | GCCCCGCGAAAGAGCGGAAG |
DRP1 | AAGAACCAACCACAGGCAAC | GTTCACGGCATGACCTTTTT |
FIS1 | CTTGCTGTGTCCAAGTCCAA | GCTGAAGGACGAATCTCAGG |
MFN1 | TTGGAGCGGAGACTTAGCAT | TTCGATCAAGTTCCGGATTC |
MFN2 | AGAGGCATCAGTGAGGTGCT | GCAGAACTTTGTCCCAGAGC |
OPA1 | GGCCAGCAAGATTAGCTACG | ACAATGTCAGGCACAATCCA |
2.4. Protein Extraction and Immunoblotting
2.5. Transmission Electron Microscopy
2.6. Mitochondria Fluorescent Staining
2.7. Spheroid Formation Assay
2.8. siRNA Knockdown
2.9. Soft Agar Colony Formation Assay
2.10. Isolation of Mitochondria
2.11. Cellular ATP Levels
2.12. Blue Native Gel Electrophoresis (BNGE)
2.13. Mitochondrial Respiratory Complex Activities
2.14. Statistical Analysis
3. Results
3.1. CSCs Present Increased Mitochondrial Mass
3.2. Mitochondrial Fusion Is Increased in CSCs
3.3. OPA1 Modulates the Tumorsphere Formation
3.4. CSCs Show Modulation of Mitochondrial Respiratory Complex Amounts, Activity, and Assembly into Supercomplexes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Carmona-Carmona, C.A.; Dalla Pozza, E.; Ambrosini, G.; Cisterna, B.; Palmieri, M.; Decimo, I.; Cuezva, J.M.; Bottani, E.; Dando, I. Mitochondrial Elongation and OPA1 Play Crucial Roles during the Stemness Acquisition Process in Pancreatic Ductal Adenocarcinoma. Cancers 2022, 14, 3432. https://doi.org/10.3390/cancers14143432
Carmona-Carmona CA, Dalla Pozza E, Ambrosini G, Cisterna B, Palmieri M, Decimo I, Cuezva JM, Bottani E, Dando I. Mitochondrial Elongation and OPA1 Play Crucial Roles during the Stemness Acquisition Process in Pancreatic Ductal Adenocarcinoma. Cancers. 2022; 14(14):3432. https://doi.org/10.3390/cancers14143432
Chicago/Turabian StyleCarmona-Carmona, Cristian Andres, Elisa Dalla Pozza, Giulia Ambrosini, Barbara Cisterna, Marta Palmieri, Ilaria Decimo, José M. Cuezva, Emanuela Bottani, and Ilaria Dando. 2022. "Mitochondrial Elongation and OPA1 Play Crucial Roles during the Stemness Acquisition Process in Pancreatic Ductal Adenocarcinoma" Cancers 14, no. 14: 3432. https://doi.org/10.3390/cancers14143432