Bladder cancer (BCa), one of the most common and deadly malignancies of the urinary system, is characterized by high rates of recurrence and rapid progression. Exosomes and long non-coding RNAs (lncRNAs) are key players in tumor development, with lncRNAs comprising 3.36% of the total RNA content in exosomes. Although exosomal lncRNAs are essential regulators of BCa, their underlying mechanisms remain poorly understood.

This research published in the Genes & Diseases journal by a team from Wuhan University evaluated the role of exosomal lnc-TAF12–2:1 in the promotion of BCa.

The research team performed lncRNA chip sequencing of urinary exosome RNA collected from BCa patients and identified lnc-TAF12–2:1 as highly expressed in these patients. Functional assays revealed that silencing of lnc-TAF12–2:1 inhibited tumor growth, enhanced cell cycle arrest, and induced apoptosis, while its overexpression had the opposite effect—both in vitro and in xenograft mouse models. Interestingly, the researchers found that exosomal lnc-TAF12–2:1 exerted its function through exosomal intercellular transmission.

Further analysis showed lnc-TAF12–2:1 to be predominantly localized in the cytoplasm and tends to form a competing endogenous RNA (ceRNA) regulatory network. A dual luciferase reporter assay, RIP, and RNA pulldown assays confirmed the interaction of lnc-TAF12–2:1, miR-7847–3p, and ASB12. Similar to lnc-TAF12–2:1, down-regulation of ASB12 expression repressed BCa cell proliferation and migration, while promoting cell cycle arrest at the G0/G1 phase and inducing apoptosis. Mechanistically, exosomal lnc-TAF12–2:1 acted as a sponge for miR-7847–3p, alleviating miRNA-mediated silencing of ASB12 and thereby promoting BCa progression.

Importantly, this study also confirmed that ASB12 functions as an oncogene, promoting cell proliferation and migration while inhibiting cell cycle arrest and apoptosis.

In conclusion, this study suggests that exosomal lnc-TAF12–2:1 is a novel diagnostic and therapeutic biomarker that functions by influencing the miR-7847–3p/ASB12 regulatory axis in BCa.

Reference

Title of Original Paper: Urinary exosomal lnc-TAF12–2:1 promotes bladder cancer progression through the miR-7847–3p/ASB12 regulatory axis

Journal: Genes & Diseases
Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

DOI: https://doi.org/10.1016/j.gendis.2024.101384

Funding Information:

Wuhan University (No. 4206–413100049)
The Science and Technology Department of Hubei Province Key Project (China) (No. 2022EJD001)
Zhongnan Hospital of Wuhan University (No. ZNYQ2023002, KY0100000109)
The Fundamental Research Funds for the Central Universities (China) (No. 2042022dx0003)
Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2020-PT320-004)
Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (No. 2022QNRC001).

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

Scopus CiteScore: 7.3 | Impact Factor: 6.9

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