OTUB1 (OTU Deubiquitinase, Ubiquitin Aldehyde Binding 1)

This study highlights the pro-tumor role of OTUB1/SLC7A11 in ovarian cancer through the activation of the PI3K/AKT signaling pathway, offering new insights into potential targeted therapies for ovarian cancer.

OTUB1 inhibits ferroptosis and sustains CSC-like features in BCa by deubiquitinating and stabilising SLC7A11. The OTUB1-SLC7A11 axis represents a novel regulatory mechanism of CSC maintenance and may serve as an intervention point in BCa.

OTUB1 in turn stabilized SLC7A11 expression by deubiquitination. Overexpression of either KIAA1429 or OTUB1 partially reversed the pro-ferroptotic effect induced by FEZF1-AS1 inhibition in MM cells.

These findings demonstrate that the loss of OTUB1 promotes ferroptosis in pancreatic β-cells through destabilization of SLC7A11. Targeting the OTUB1-SLC7A11 pathway may offer a novel therapeutic approach for preserving β-cell survival and preventing the progression of diabetes.

In addition, a small-molecule OTUB1 inhibitor combined with gemcitabine treatment could synergistically inhibit tumor growth in high-OTUB1-expressing murine tumoroids. Collectively, OTUB1 could impart gemcitabine resistance by promoting de novo pyrimidine synthesis, and targeted suppression of OTUB1 could be an effective strategy to overcome gemcitabine resistance in PC.

ART exerted potent anti-OC effects by targeting GP130Lys250, disrupting IL-6/STAT3 signaling, downregulating OTUB1, promoting SLC7A11 degradation, and triggering ferroptosis. The identification of GP130Lys250 as ART's precise binding site and the novel IL-6/STAT3/OTUB1/SLC7A11 axis represent significant mechanistic innovations. ART is a highly promising and safe candidate for OC therapy.

Our study demonstrated that XHP may exert anti-TNBC effects partly by inhibiting OTUB1-mediated deubiquitination of SLC7A11, thereby inducing system Xc-/GPX4 axis-dependent ferroptosis. This study provides a foundation for developing potential products from XHP plant materials for the TNBC treatment.

This study identifies OTUB1 as a novel regulator of ferroptosis in CRC through the stabilization of GPX4. Targeting the OTUB1-GPX4 axis may provide a new therapeutic approach for inducing ferroptosis in CRC cells, potentially overcoming resistance to conventional therapies and improving patient outcomes.

Our findings indicate that Hypo-exos inhibit ferroptosis to augment drug resistance in melanoma by delivering HIF-1α to modulate the p53/OTUB1/SLC7A11 axis. Exosomal HIF-1α may represent a promising biomarker and therapeutic target for addressing drug resistance in melanoma.

In this study, an HT-29 xenograft mouse model demonstrated that curcumol combined with oxaliplatin significantly suppressed tumor growth (Ki67↓) and microvessel density (CD31↓)...OTUB1 overexpression activated the TGFB1/VEGF axis, enhancing cell invasiveness and angiogenesis-effects reversed by high-dose curcumol. These findings identify the OTUB1-TGFB1/VEGF axis as a key target of curcumol in inhibiting colon cancer angiogenesis, elucidating its anti-tumor mechanism and offering a novel therapeutic strategy for targeted treatment.

Inhibition of EZH2 with either DZNep or EPZ6438, EZH2 inhibitors, or siRNA significantly decreased the proliferative and metastatic capacity of NSCLC cells induced by nicotine treatment...Furthermore, the c-Myc inhibitor 10058-F4 exhibited synergistic effects with the EZH2 inhibitor DZNep in suppressing NSCLC cell proliferation and metastasis both in vitro and in vivo.Nicotine regulates the c-Myc/EZH2 signaling pathway via OTUB1-mediated deubiquitination, thereby promoting the proliferation and metastasis of NSCLC cells. This research reveals novel molecular mechanisms of nicotine in the development of NSCLC, providing a theoretical foundation for future therapeutic strategies.

OTUB1 plays a critical role in glioma progression and may serve as a novel therapeutic target. The development of inhibitors targeting OTUB1 could potentially improve outcomes for glioma patients.