bims-micpro 2024-07-21 papers

Issue of 2024‒07‒21
five papers selected by
Thomas Farid Martínez, University of California, Irvine

Cancer Cell Int. 2024 Jul 19. 24(1): 252

Current understanding of functional peptides encoded by lncRNA in cancer.

Hua Tian, Lu Tang, Zihan Yang, Yanxi Xiang, Qi Min, Mengshuang Yin, Huili You, Zhangang Xiao, Jing Shen.

Dysregulated gene expression and imbalance of transcriptional regulation are typical features of cancer. RNA always plays a key role in these processes. Human transcripts contain many RNAs without long open reading frames (ORF, > 100 aa) and that are more than 200 bp in length. They are usually regarded as long non-coding RNA (lncRNA) which play an important role in cancer regulation, including chromatin remodeling, transcriptional regulation, translational regulation and as miRNA sponges. With the advancement of ribosome profiling and sequencing technologies, increasing research evidence revealed that some ORFs in lncRNA can also encode peptides and participate in the regulation of multiple organ tumors, which undoubtedly opens a new chapter in the field of lncRNA and oncology research. In this review, we discuss the biological function of lncRNA in tumors, the current methods to evaluate their coding potential and the role of functional small peptides encoded by lncRNA in cancers. Investigating the small peptides encoded by lncRNA and understanding the regulatory mechanisms of these functional peptides may contribute to a deeper understanding of cancer and the development of new targeted anticancer therapies.

Keywords: Cancer; Coding potential; Functional peptides; Small ORF; lncRNA

DOI: https://doi.org/10.1186/s12935-024-03446-7

Cell Biol Int. 2024 Jul 15.

Microproteins/micropeptides dysregulation contributes to cancer progression and development: A mechanistic review.

Paul Rodrigues, Harun Bangali, Eyhab Ali, M K Sharma, Bekhzod Abdullaev, Adnan Taan Alkhafaji, Maha Medha Deorari, Rahman S Zabibah, Ali Haslany.

Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives.

Keywords: cancer; drug resistance; metastasis; micropeptide; microprotein

DOI: https://doi.org/10.1002/cbin.12219

Elife. 2024 Jul 16. pii: RP90713. [Epub ahead of print]12

Translational regulation enhances distinction of cell types in the nervous system.

Toshiharu Ichinose, Shu Kondo, Mai Kanno, Yuichi Shichino, Mari Mito, Shintaro Iwasaki, Hiromu Tanimoto.

Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically defined cells in the Drosophila brain, we here revealed substantial post-transcriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias toward the 5' leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open-reading frames in the 5' leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.

Keywords: D. melanogaster; cell biology; glia; neuron; neuroscience; ribo-seq; translational efficiency; upstream open-reading frame

DOI: https://doi.org/10.7554/eLife.90713

Amino Acids. 2024 Jul 15. 56(1): 45

The short peptide encoded by long non-coding RNA RNF217-AS1 inhibits stomach cancer tumorigenesis, macrophage recruitment, and pro-inflammatory responses.

Qi Ma, Fei Ma, Bin Zhang, Yonglei Zhang, Liangqun Peng, Xiangnan Li.

Certain long non-coding RNAs (lncRNAs) have potential peptide-coding abilities. Here, the role and molecular basis of the RNF217-AS1-encoded peptide in stomach cancer (SC) tumorigenesis were explored. Here, lncRNAs associated with SC pathogenesis and macrophage infiltration and lncRNAs with peptide-coding potential were searched by bioinformatics analysis. The gene mRNA and protein levels were examined by RT-qPCR and western blot assays, respectively. Cell viability, migratory, and invasive abilities were measured by CCK-8, Transwell migration, and Transwell invasion assays, respectively. The potential biological processes related to lncRNA RNF217-AS1 were identified by single-gene GSEA analysis. The effect of RNF217-AS1-encoded peptide on SC tumorigenesis was examined by mouse xenograft experiments. The results showed that lncRNA NR2F1-AS1 and RNF217-AS1 were differentially expressed and associated with macrophage infiltration in SC, and they had the ability to translate into short peptides. The RNF217-AS1 ORF-encoded peptide could reduce SC cell viability, inhibit cell migration and invasion, as well as hinder the development of SC xenograft tumors. The RNF217-AS1 ORF-encoded peptide in human SC AGS cells suppressed THP-1 cell migration, triggered the differential expression of CXCL1/CXCL2/CXCL8/CXCL12, and inactivated the TLR4/NF-κB/STAT1 signaling pathways. As a conclusion, the RNF217-AS1 ORF-encoded peptide hindered SC progression in vitro and in vivo and suppressed macrophage recruitment and pro-inflammatory responses in SC.

Keywords: Inflammation; Macrophage; Peptide; RNF217-AS1; Stomach cancer; lncRNA

DOI: https://doi.org/10.1007/s00726-024-03404-7

Allergol Int. 2024 Jul 17. pii: S1323-8930(24)00048-0. [Epub ahead of print]

A micropeptide TREMP encoded by lincR-PPP2R5C promotes Th2 cell differentiation by interacting with PYCR1 in allergic airway inflammation.

Zhengxia Wang, Xinyu Jia, Wei Sun, Min Wang, Qi Yuan, Tingting Xu, Yanan Liu, Zhongqi Chen, Mao Huang, Ningfei Ji, Mingshun Zhang.

BACKGROUND: Allergic asthma is largely dominated by Th2 lymphocytes. Micropeptides in Th2 cells and asthma remain unmasked. Here, we aimed to demonstrate a micropeptide, T-cell regulatory micropeptide (TREMP), in Th2 cell differentiation in asthma.METHODS: TREMP translated from lincR-PPP2R5C was validated using Western blotting and mass spectrometry. TREMP knockout mice were generated using CRISPR/Cas9. Coimmunoprecipitation revealed that TREMP targeted pyrroline-5-carboxylate reductase 1 (PYCR1), which was further explored in vitro and in vivo. The levels of TREMP and PYCR1 in Th2 cells from clinical samples were determined by flow cytometry.
RESULTS: TREMP, encoded by lincR-PPP2R5C, was in the mitochondrion. The lentivirus encoding TREMP promoted Th2 cell differentiation. In contrast, Th2 differentiation was suppressed in TREMP-/- CD4+ T cells. In the HDM-induced model of allergic airway inflammation, TREMP was increased in pulmonary tissues. Allergic airway inflammation was relieved in TREMP-/- mice treated with HDM. Mechanistically, TREMP interacted with PYCR1, which regulated Th2 differentiation via glycolysis. Glycolysis was decreased in Th2 cells from TREMP-/- mice and PYCR1-/- mice. Similar to TREMP-/- mice, allergic airway inflammation was mitigated in HDM-challenged PYCR1-/- mice. Moreover, we measured TREMP and PYCR1 in asthma patients. And we found that, compared with those in healthy controls, the levels of TREMP and PYCR1 in Th2 cells were significantly increased in asthmatic patients.
CONCLUSIONS: The micropeptide TREMP encoded by lincR-PPP2R5C promoted Th2 differentiation in allergic airway inflammation by interacting with PYCR1 and enhancing glycolysis. Our findings highlight the importance of neglected micropeptides from noncoding RNAs in allergic diseases.

Keywords: Allergic asthma; Allergic inflammation; Animal model; House dust mites; Th2

DOI: https://doi.org/10.1016/j.alit.2024.04.004