PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1)

Notably, we highlight the potential regulatory role of ANK2 in the progression of CRC. This research provides theoretical support and new directions for early screening, diagnostic biomarker identification, and targeted therapy strategies for CRC.

Finally, we investigated the expression of NETosis-related genes in single-cell subtypes and in the HepG2 cell line, providing further insights into their relevance in HCC. Overall, this NETosis-related gene signature serves as a prognostic indicator and a potential predictor for immunotherapy response in HCC.

KRAS inhibitors, including KRAS G12D inhibitor MRTX1133, are promising therapeutics against KRAS-mutated pancreatic ductal adenocarcinoma (PDAC), but drug resistance limits their efficacy. Our study reveals that robust induction of apoptosis using a combination of BCL-xL PROTAC degrader and an mTOR inhibitor, significantly enhances MRTX1133 efficacy in PDAC models without increasing toxicity to normal tissues.

Upregulation of PMAIP1 promotes apoptosis by increasing the Bax/Bcl-2 ratio, induces DNA damage, elevates ROS levels, and reduces ATP, mtDNA, and JC-1 levels, leading to mitochondrial dysfunction; conversely, knockdown of PMAIP1 alleviates these changes. PMAIP1 exerts a tumor suppressor effect by regulating apoptosis, DNA damage, and mitochondrial dysfunction, providing potential target support for the treatment of TNBC.

Furthermore, reducing PMAIP1 expression has been shown to hinder the proliferation, metastasis, and stemness of LUAD cells. In summary, our findings indicate that PMAIP1 has potential as a prognostic biomarker and a target for immunotherapy in patients with LUAD.

AKT-100 is also synergistic with the PARP inhibitor olaparib and with chemotherapy by inhibiting alternative DNA repair mechanisms associated with resistance to standard therapies. RNA sequencing confirms that AKT-100 reactivates wild type p53-driven expression of genes associated with normal cell cycle regulation (induction of CDKN1A encoding p21 and GADD45A ), apoptosis (induction of PMAIP1 encoding Noxa and DR5 encoding Death Receptor 5), and inhibits DNA replication and repair in cancer cells. Thus, p53 reactivators under development, such as AKT-100, hold promise as novel therapeutic agents to directly target missense mutant, gain of oncogenic function p53.

NCL plays a critical role in regulating the proliferation, apoptosis, and cell cycle progression of Kasumi-1 cells. The mechanism likely involves suppressing cell cycle progression through activation of the TP53-CDKN1A pathway and promoting apoptosis by upregulating apoptosis-related genes.

Importantly, LD-110 demonstrated a good in vivo pharmacokinetic profile and effectively inhibited in vivo tumor growth in breast and lung xenograft tumor models. Collectively, we discovered a potent PROTAC degrader targeting LSD1 with effective anti-cancer activity for future development as a promising anti-cancer agent.

Utilizing a multi-model synergistic artificial intelligence framework, we demonstrated the remarkable potential of PCD to provide individualized vulnerability assessments and customized recommendations for metabolic and immunotherapeutic interventions in OA. We identified abnormal expression of four hub genes associated with PCD and examined their biological functions, thereby facilitating new avenues for research into the role of PCD in OA and other immune-mediated diseases.

These findings indicate that γT3 and δT3 inhibit HCC2998 cell proliferation by activating the DDR pathway, highlighting their potential as therapeutic agents to overcome cell cycle arrest resistance in CRC. This study provides critical insights into the molecular actions of γT3 and δT3, supporting their further investigation as promising candidates for CRC intervention.

A total of 41 drugs were predicted to have potential therapeutic effects, including omarigliptin, bepridil and bortezomib. Finally, qRT-PCR validation demonstrated that SLC26A4, KCNQ1, PMAIP1, DPP4, and NOX4 had expression trends consistent with public database results. This study identified 6 MDRGs (SLC26A4, SLC25A37, KCNQ1, PMAIP1, DPP4 and NOX4) associated with the prognosis of DDTC, providing valuable scientific insights and references for the targeted therapy and patient stratification of DDTC.