MIR4435-2HG (MIR4435-2 Host Gene)

This multi-omics analysis reveals that the development of sessile serrated adenomas and conventional adenomas (CA) is associated with distinct epithelial origins, with serrated lesions linked to SSC cells and CA linked to ASC cells. These lesion-specific molecular features provide a mechanistic basis for improving preoperative detection and for developing adjunct molecular tools for high-risk polyp assessment.

Although current research remains exploratory, lncRNAs show significant promise as predictive biomarkers and therapeutic targets. Future personalized strategies intergrating lncRNA profiles could help overcome drug resistance and improve patient outcomes.

Our findings identify a previously uncharacterized MIR4435-2HG/miR-29c-3p/FSP1 axis that promotes lenvatinib resistance by inhibiting ferroptosis, highlighting that targeting this axis may provide a mechanistic basis and preclinical rationale for overcoming lenvatinib resistance in HCC.

Furthermore, a potential MIR4435-2HG/hsa-miR-125a-5p/NPM1 ceRNA axis was identified. Collectively, these findings indicate that NPM1 contributes to ESCA progression via metabolic modulation and ceRNA regulation, supporting its utility as a prognostic biomarker and therapeutic target.

In addition, recipient tumor cells internalized EV-packaged MIR4435-2HG and simultaneously secreted chemokines to recruit monocytes, establishing a potential feed-forward loop between M2 macrophages and tumor cells. This study identified EV-packaged MIR4435-2HG as a crucial bladder cancer marker that mediates intercellular communication during cigarette smoke exposure, suggesting a promising approach for bladder cancer prevention and treatment.

Furthermore, breast cancer cell-derived exosomes deliver MIR4435-2HG to TAMs, promoting M2 polarization through C/EBPβ activation, which further exacerbates cancer progression. Collectively, our findings unveil a novel MIR4435-2HG/miR-205-5p/UBE2N ceRNA network that drives breast cancer progression and highlights exosomal MIR4435-2HG as a critical mediator of TAM polarization, offering potential as a potential biomarker and therapeutic target for breast cancer.

Panobinostat, Pirinixic acid, and Fluorouracil were predicted to be the potential BCL2L12-targeted drug for HCC. Our findings offer an understanding of the Oncogenic Role of BCL2L12 associated with immune status in the prognosis of HCC and provide potential strategies for currently limited treatment.

MIR4435-2HG may represent a potential biomarker associated with metastasis and poor prognosis. Its possible involvement in the PI3K-Akt pathway warrants further validation and investigation in larger clinical cohorts.

The ferroptosis activator RSL3 further attenuated tumor progression in both the knockdown and overexpression models, and combined treatment with the ERK inhibitor SCH772984 synergistically suppressed tumor growth in MIR4435-2HG-overexpressing xenografts. Notably, RSL3 diminished IQGAP3, Ras, ERK, CREB, and GPX4 levels across the experimental conditions. These findings indicate that MIR4435-2HG is a pivotal regulator of bladder cancer progression and ferroptosis via the IQGAP3/Ras/ERK/CREB axis, suggesting that MIR4435-2HG is a potential therapeutic target for intervention.

MRlncRNAs, particularly MIR4435-2HG, contribute to HCC progression and an immunosuppressive tumor microenvironment. This study establishes a robust prognostic model and identifies potential targets for precision immunotherapy in HCC.

Additionally, P65, a component of the NF-κB pathway, directly promotes MIR4435-2HG transcription, triggering subsequent chemoresistance. Based on these results, MIR4435-2HG is recognized as a reliable prognostic marker and serves as a target for therapeutic strategies, presenting new approaches to counteract L-OHP resistance and enhance CRC patient outcomes.

The model we developed was a powerful predictive tool for BLCA prognosis and revealed the impact of mitotic catastrophe heterogeneity on BLCA in multiple dimensions, which then guided clinical decision-making. Furthermore, we highlighted the potential of ANLN as a BLCA target.