February 23rd, 2025
Recent Publications Harnessing the Power of Translatomics
Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.
In this week’s Sunday papers,
- Chen et al. used ribosome profiling to determine the translation of HDSP microprotein for gastric cancer progression.
- Qiao et al. employed ribosome profiling to identify that circular RNA circR-127aa in gastric cancer bound to specific microRNA to promote tumor suppression.
- Zheng et al. used ribosome profiling to confirm that ALKBH5 regulated the translation of oncogenic WRAP53 isoforms.
The microprotein HDSP promotes gastric cancer progression through activating the MECOM-SPINK1-EGFR signaling axis
Nature Communications, 2024
Chen, Y., Li, Q., Yu, X., Lu, L., Zhou, Z., Li, M., Xia, R., Gan, X., Hu, Y., Guo, G. and Guo, J.
Gastric cancer (GC) is a highly aggressive malignancy and a leading cause of cancer-related deaths worldwide. It is characterized by late diagnosis, limited treatment options, and poor prognosis. The paper highlights the critical role of molecular mechanisms driving GC progression, focusing on the microprotein HDSP. HDSP is found to be overexpressed in GC tissues and associated with tumour growth, invasion, and metastasis. Ribosome profiling was used to identify the translation of HDSP.
HDSP activates the MECOM-SPINK1-EGFR signaling axis, which drives GC progression. HDSP was found to upregulate a transcriptional regulator, MECOM (EVI1). It upregulates SPINK1, a serine protease inhibitor linked to cancer cell survival. This cascade activates EGFR (Epidermal Growth Factor Receptor) signaling, promoting cell proliferation, invasion, and resistance to apoptosis.
Experimental evidence from cell-based assays, patient-derived samples, and mouse models confirmed that HDSP overexpression correlates with poor prognosis in GC patients. Inhibiting HDSP or disrupting its downstream signaling components, such as SPINK1 or EGFR, significantly reduced tumor progression, highlighting potential therapeutic targets.
This study sheds light on the oncogenic role of HDSP and its regulatory network in gastric cancer, suggesting that targeting the HDSP-MECOM-SPINK1-EGFR axis could be a promising strategy for GC treatment.
Learn more about EIRNA Bio’s ribosome profiling service here.
Inhibitory effects of circR-127aa on gastric cancer progression and tumor growth
Cellular Signalling, 2024
Qiao, L., Pan, W., Yang, J., Cheng, Y., Han, Y., Zhu, Q., Liu, R., Zhang, H. and Ba, Y.
This paper explores the tumor-suppressive role of circR-127aa, a circular RNA (circRNA), in gastric cancer (GC). The authors found that circR-127aa is significantly downregulated in GC tissues and cell lines, suggesting its potential as a tumor suppressor.
circR-127aa functions by interacting with key oncogenic pathways to inhibit tumor progression. Using ribosome profiling, it was shown to bind to specific microRNAs (miRNAs), preventing them from suppressing tumor-suppressor genes. This leads to the downregulation of oncogenic signaling pathways involved in GC proliferation, migration, and invasion. Ribosome profiling showed that circR-127aa enhances the translation of these tumor-suppressive proteins. The assay confirmed that circR-127aa overexpression significantly reduced GC cell growth and metastasis in both in vitro and in vivo models.
The study revealed that low circR-127aa expression correlates with poor prognosis, highlighting its potential as a diagnostic biomarker. It suggests that restoring circR-127aa expression or targeting its regulatory network could serve as a novel therapeutic approach for GC treatment. Overall, this finding emphasizes the critical role of circRNAs in cancer progression and provides new insights into the molecular mechanisms underlying GC, paving the way for potential RNA-based therapies.
Learn more about EIRNA Bio’s ribosome profiling service here.
ALKBH5 suppresses gastric cancer tumorigenesis and metastasis by inhibiting the translation of uncapped WRAP53 RNA isoforms in an m6A-dependent manner
Molecular Cancer, 2025
Zheng, Z., Lin, F., Zhao, B., Chen, G., Wei, C., Chen, X., Nie, R., Zhang, R., Zhao, Z., Zhou, Z. and Li, Y.
ALKBH5 is an m6A demethylase that has a tumor-suppressive role in gastric cancer (GC). Zheng et al. found that ALKBH5 is significantly downregulated in GC tissues, and its loss is associated with increased tumor growth and metastasis.
The demethylase removes m6A modifications from uncapped WRAP53 RNA isoforms, preventing their efficient translation. WRAP53, known for its role in RNA processing and telomere maintenance, was found to have oncogenic isoforms that promote GC progression when translated. By inhibiting their translation, ALKBH5 reduces GC cell proliferation, invasion, and metastatic potential.
The authors used ribosome profiling and RNA sequencing to confirm that ALKBH5 directly regulates the translation of these oncogenic WRAP53 isoforms. Supported by the patient data analysis, it revealed that low ALKBH5 expression correlates with poor prognosis, highlighting its potential as a biomarker and therapeutic target.
This study underscores the critical role of m6A-dependent translational control in cancer biology and suggests that restoring ALKBH5 function or targeting WRAP53 isoform translation could be a promising strategy for GC treatment.
Learn more about EIRNA Bio’s ribosome profiling and RNA-sequencing services here.