22 April 2020 : Clinical Research
Prohibitin 2/PHB2 in Parkin-Mediated Mitophagy: A Potential Therapeutic Target for Non-Small Cell Lung Carcinoma
Han Zhang1ABCDEF, Chuntong Yin1ABCDEF, Xin Liu2ADEFG, Xue Bai2BCDE, Lei Wang2BCDE, Honglin Xu2BCDE, Jin Ju2BCDE, Linyou Zhang1ABCDEFG*DOI: 10.12659/MSM.923227
Med Sci Monit 2020; 26:e923227
Abstract
BACKGROUND: Mitophagy, a selective autophagy process, plays various roles in tumors. Prohibitin 2 (PHB2) is an inner-mitochondrial membrane protein that participates in parkin-induced mitophagy. However, the role of PHB2 in non-small cell lung carcinoma (NSCLC) has not been previously reported.
MATERIAL AND METHODS: PHB2 protein or PHB2-mRNA in NSCLC and paired normal tissues was determined by Western blot, qRT-PCR, and immunohistochemical staining. Cell proliferation was detected by CCK-8 assay. Cell migration was evaluated by wound healing and transwell migration assays. A 3D live-cell confocal system was used to monitor autophagic flux. Mitochondrial autolysosomes were observed by transmission electron microscopy (TEM). Finally, we performed JC-1 assay to measure mitochondrial membrane potential (MMP).
RESULTS: The level of PHB2 was significantly increased in human NSCLC specimens compared to paired adjacent specimens. Inhibition of PHB2 expression attenuated mitophagy in A549 and H1299 cells, as indicated by decreased levels of LC3 II/I and parkin markers and increased level of p62 protein. Furthermore, the inhibition caused reduction in mitochondrial autolysosomes and autophagic flux, as shown by TEM and live-cell imaging, respectively. In addition, PHB2 inhibition caused a remarkable increase in MMP and suppressed the proliferation and migration of A549 and H1299 cells.
CONCLUSIONS: Our results suggest that downregulation of PHB2 reduced parkin-mediated mitophagy, which suppressed proliferation and migration of A549 and H1299 cells.
Keywords: Cell Migration Inhibition, Membrane Proteins, Mitochondrial Degradation, Aged, 80 and over, Membrane Potential, Mitochondrial, Mitochondria, Prohibitins, Repressor Proteins
Errate
The authors requested replacing Figure 2 as there was an error. The details of this error are as follows: Representative picture of transwell migration assay, A549 control group (Figure 2E). Representative picture of wound healing assay, 24h, A549 negative control group (Figure 2C). The above pictures were repeated within their own group (control group and negative control group). Representative picture of wound healing assay, 0h, A549 si-PHB2 group (Figure 2C). The authors used the wrong picture during data handling. Changes do not influence the results of the paper. In the original experiment, H1299 and A549 cells were divided into 4 groups (Control, si-PHB2, +PHB2, and negative control). Transwell migration assay and wound healing assay were performed 5 times. In addition, these results have been repeated by another research group (PHB2 promotes tumorigenesis via RACK1 in non-small cell lung cancer, Theranostics 2021, Vol. 11, Issue 7).
Reference: Han Zhang, Chuntong Yin, Xin Liu, Xue Bai, Lei Wang, Honglin Xu, Jin Ju, Linyou Zhang. Prohibitin 2/PHB2 in Parkin-Mediated Mitophagy: A Potential Therapeutic Target for Non-Small Cell Lung Carcinoma. Med Sci Monit. 2020; 26: e923227. DOI: 10.12659/MSM.923227
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
05 Mar 2024 : Clinical Research
Role of Critical Shoulder Angle in Degenerative Type Rotator Cuff Tears: A Turkish Cohort StudyMed Sci Monit In Press; DOI: 10.12659/MSM.943703
06 Mar 2024 : Clinical Research
Comparison of Outcomes between Single-Level and Double-Level Corpectomy in Thoracolumbar Reconstruction: A ...Med Sci Monit In Press; DOI: 10.12659/MSM.943797
21 Mar 2024 : Meta-Analysis
Economic Evaluation of COVID-19 Screening Tests and Surveillance Strategies in Low-Income, Middle-Income, a...Med Sci Monit In Press; DOI: 10.12659/MSM.943863
10 Apr 2024 : Clinical Research
Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Dep...Med Sci Monit In Press; DOI: 10.12659/MSM.942612
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952