LncRNA-mediated organization of oncogenic chromatin state is a targetable vulnerability in leukemia

The lncRNA CTD-2566 J3.1 orchestrates oncogenic gene regulation via chromatin interactions in luminal breast cancer.

These findings establish CTD-2566 J3.1 as a multifunctional enhancer-associated lncRNA (e-lncRNA) that orchestrates key oncogenic processes in luminal breast cancer and underscores the utility of three-dimensional culture systems to reveal context-specific lncRNA functions.

The Mechanisms Underlying the Aberrant Expression and Oncogenic Role of SNHG1 in Cancer

A mechanism-driven approach is adopted to systematically examine SNHG1 dysregulation and its roles in cancer, which complements existing literature and provides a clear framework for future SNHG1 research.

Rbm5 sustains leukemia stem cells through a Myc-driven transcriptional circuitry.

Acute myeloid leukemia (AML) represents a type of malignant hematological disease that is usually caused by the dysregulated developmental program of leukemia stem cells (LSCs). Here, we report that an unappreciated RNA-binding protein, Rbm5, selectively promotes murine leukemogenesis, maintains LSC self-renewal in vivo, and is dispensable for normal hematopoiesis. Rbm5 is highly expressed in LSCs, and its deficiency results in specifically defective LSC function, along with inhibition of self-renewal gene expression and induction of myeloid differentiation. Multi-disciplinary mechanistic investigations further identified Myc as the major and direct transcriptional target of Rbm5 in primary leukemia cells. Moreover, RBM5 not only interacts with MYC but also maintains its protein levels, thereby sustaining the Myc downstream transcriptional network through its proper genome-wide occupancy. Forced expression of Myc sufficiently rescued the Rbm5-depleted LSC defects. Thus, our study demonstrates that Rbm5 regulates the AML LSC program through non-canonical transcriptional mechanisms, providing a strong rationale for targeting Rbm5 therapeutically. In Brief. Zhang et al. illustrate the role of Rbm5 in sustaining the self-renewal program in leukemia stem. cells (LSCs) primarily through the Myc transcriptional network. Specifically, Rbm5 loss results in a significant decrease in Myc protein levels, thereby disrupting. the Myc downstream transcriptional network in LSCs. Notably, this effect is specific to LSCs, as. normal hematopoietic stem cells (HSCs) do not exhibit such changes upon Rbm5 loss.

Integrative Pan-Cancer Characterization of lncRNA UPK1A-AS1 and Its Role in Hypoxia-Associated Sorafenib Resistance in Hepatocellular Carcinoma.

Investigating the mechanism of lncRNA SChLAP1 in prostate cancer

A mechanism wherein SChLAP1 modulates AR signaling to promote PCa growth and progression is suggested, suggesting its molecular mechanism and potential to be used as a therapeutic target or biomarker.

Dark matter matters: from noncoding RNA regulation to cancer immunity

These findings call for a revised molecular dogma in which the noncoding genome is recognized as a major regulator of cellular function, oncogenic transformation, and immune surveillance.