bims-micpro 2023-06-18 papers

Issue of 2023‒06‒18
two papers selected by
Thomas Farid Martínez
University of California, Irvine

Cancer Res. 2023 Jun 16. pii: CAN-23-0337. [Epub ahead of print]

Hypoxia-responsive lncRNA AC115619 encodes a micropeptide that suppresses m6A modifications and hepatocellular carcinoma progression.

Qiangnu Zhang, Teng Wei, Lesen Yan, Siqi Zhu, Wen Jin, Yu Bai, Yuandi Zeng, Xiaofei Zhang, Zexin Yin, Jilin Yang, Wenjian Zhang, Meilong Wu, Yusen Zhang, Liping Liu.

Long non-coding RNAs (lncRNAs) regulate a number of aspects of cancer biology. Recent research has shown that lncRNAs can encode micropeptides that mediate their functions in tumors. Here, we revealed that the liver-specific putative lncRNA, AC115619, is expressed at low levels in hepatocellular carcinoma (HCC) and encodes a micropeptide, designated as AC115619-22aa. AC115619 played a crucial role in the regulation of tumor progression and was a prognostic indicator in HCC. The encoded micropeptide AC115619-22aa inhibited the progression of HCC by binding to WTAP and impeding the assembly of the N6-methyladenosine (m6A) methyltransferase complex, which regulates the expression of tumor-associated genes, such as SOCS2 and ATG14. AC115619 was co-transcribed with the adjacent upstream coding gene APOB, and hypoxia induced transcriptional repression of both APOB and AC115619 by controlling HIF1A/HDAC3 and HNF4A signaling. In animal and patient-derived models, AC115619-22aa reduced global m6A levels and suppressed tumor growth. In conclusion, this study establishes AC115619 and its encoded micropeptide as potential prognostic markers and therapeutic targets for patients with HCC.

DOI: https://doi.org/10.1158/0008-5472.CAN-23-0337

Mitochondrion. 2023 Jun 10. pii: S1567-7249(23)00052-1. [Epub ahead of print]71 76-82

MOTS-c: A potential anti-pulmonary fibrosis factor derived by mitochondria.

Zewei Zhang, Dongmei Chen, Kaili Du, Yaping Huang, Xingzhe Li, Quwen Li, Xiaoting Lv.

Pulmonary fibrosis (PF) is a serious lung disease characterized by diffuse alveolitis and disruption of alveolar structure, with a poor prognosis and unclear etiopathogenesis. While ageing, oxidative stress, metabolic disorders, and mitochondrial dysfunction have been proposed as potential contributors to the development of PF, effective treatments for this condition remain elusive. However, Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), a peptide encoded by the mitochondrial genome, has shown promising effects on glucose and lipid metabolism, cellular and mitochondrial homeostasis, as well as the reduction of systemic inflammatory responses, and is being investigated as a potential exercise mimetic. Additionally, dynamic expression changes of MOTS-c have been closely linked to ageing and ageing-related diseases, indicating its potential as an exercise mimetic. Therefore, the review aims to comprehensively analyze the available literature on the potential role of MOTS-c in improving PF development and to identify specific therapeutic targets for future treatment strategies.

Keywords: MOTS-c; Mitochondrial-derived peptide; Potential mechanisms; Pulmonary fibrosis

DOI: https://doi.org/10.1016/j.mito.2023.06.002