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Analysis of institutional authors

Beltrà, MarcAuthorZorzano, AntonioAuthorSebastian, DavidAuthor

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January 7, 2025
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BNIP3 Downregulation Ameliorates Muscle Atrophy in Cancer Cachexia

Publicated to: Cancers. 16 (24): 4133- - 2024-12-01 16(24), DOI: 10.3390/cancers16244133

Authors:

Fornelli, C; Beltrà, M; Zorzano, A; Costelli, P; Sebastian, D; Penna, F
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Affiliations

Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain - Author
Inst Salud Carlos III, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid 28029, Spain - Author
Institute for Research in Biomedicine - Author
Univ Barcelona, Inst Biomed Univ Barcelona IBUB, Barcelona 08028, Spain - Author
Univ Barcelona, Sch Pharm & Food Sci, Dept Biochem & Physiol, Barcelona 08028, Spain - Author
Univ Torino, Dept Clin & Biol Sci, I-10043 Turin, Italy - Author
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Abstract

Background and Aims: Cancer cachexia is a complex syndrome affecting most cancer patients and is directly responsible for about 20% of cancer-related deaths. Previous studies showed muscle proteolysis hyper-activation and mitophagy induction in tumor-bearing animals. While basal mitophagy is required for maintaining muscle mass and quality, excessive mitophagy promotes uncontrolled protein degradation, muscle loss and impaired function. BNIP3, a key mitophagy-related protein, is significantly increased in the muscles of both mice and human cancer hosts. This study aimed to define the potential of mitigating mitophagy via BNIP3 downregulation in preserving mitochondrial integrity, counteracting skeletal muscle loss in experimental cancer cachexia. Methods: Two in vivo gene delivery methods were performed to knock down muscle BNIP3: electroporation of a BNIP3-specific shRNA expression vector or adenovirus injection. Results: The electroporation effectively reduced muscle BNIP3 in healthy mice but was ineffective in C26 tumor-bearing mice. In contrast, adenovirus-mediated BNIP3 knockdown successfully decreased BNIP3 levels also in tumor hosts. Although BNIP3 knockdown did not impact overall on body or muscle mass, it improved muscle fiber size in C26-bearing miceh2, suggesting partial prevention of muscle atrophy. Mitochondrial respiratory chain complexes (OxPhos) and TOM20 protein levels were consistently rescued, indicating improvements in mitochondrial mass, while H2O2 levels were unchanged among the groups, suggesting that BNIP3 downregulation does not impair the endogenous control of oxidative balance. Conclusions: These findings suggest that a fine balance between mitochondrial disposal and biogenesis is fundamental for preserving muscle homeostasis and highlight a potential role for BNIP3 modulation against cancer-induced muscle wasting.
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Keywords

AutophagyBnip3Cancer cachexiaMitochondriaMitophagyMitophagy mechanismsMuscle wastinProgressio

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cancers due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-02-07:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 3.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 3 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 3.
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/2445/220113
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Italy.

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Awards linked to the item

This work was supported by Fondazione AIRC (IG 2018-ID. 21963 project, PI: F.P.) and by the University of Torino (local research funds). M.B. was supported by an AIRC Short-term Fellowship.
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