USP9X-mediated REV1 deubiquitination promotes lung cancer radioresistance via the action of REV1 as a Rad18 molecular scaffold for cystathionine γ-lyase.

Background: Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear.

CDKL1 potentiates the antitumor efficacy of radioimmunotherapy by binding to transcription factor YBX1 and blocking PD-L1 expression in lung cancer.

Background: The evasion of the immune response by tumor cells through programmed death-ligand 1 (PD-L1) has been identified as a factor contributing to resistance to radioimmunotherapy in lung cancer patients. However, the precise molecular mechanisms underlying the regulation of PD-L1 remain incompletely understood. This study aimed to investigate the role of cyclin-dependent kinase-like 1 (CDKL1) in the modulation of PD-L1 expression and the response to radioimmunotherapy in lung cancer.

Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis.

Radioresistance is a major constraint on the efficacy of lung cancer radiotherapy, but its mechanism has not been fully elucidated. Here, we found that FBXO22 was aberrantly highly expressed in lung cancer and that FBXO22 knockdown increased the radiosensitivity of lung cancer cells. Mechanistically, FBXO22 promoted Rad51 gene transcription by increasing the level of FOXM1 at the Rad51 promoter, thereby inducing the formation of lung cancer radioresistance.

OTUB1 Targets CHK1 for Deubiquitination and Stabilization to Facilitate Lung Cancer Progression and Radioresistance.

Purpose: Radioresistance of lung cancer poses a significant challenge when it comes to the treatment of advanced, recurrent, and metastatic cases. Ovarian tumor domain ubiquitin aldehyde binding 1 (OTUB1) is a key member of the deubiquitinase OTU superfamily. This protein is involved in various cellular functions, including cell proliferation, iron death, lipid metabolism, and cytokine secretion as well as immune response processes.

FIBP interacts with transcription factor STAT3 to induce EME1 expression and drive radioresistance in lung adenocarcinoma.

Cancer cells inevitably develop radioresistance during lung adenocarcinoma radiotherapy. However, the mechanisms are incompletely clarified. In this study, we show that FIBP protein expression in lung adenocarcinoma tissues is upregulated and associated with worse overall survival.

KDM4C silencing inhibits cell migration and enhances radiosensitivity by inducing CXCL2 transcription in hepatocellular carcinoma.

KDM4C, which is a histone lysine demethylase, has been proposed to participate in the malignant transformation and progression of several types of cancer. However, its roles in hepatocellular carcinoma (HCC) remain poorly understood. Here, we find that KDM4C protein expression is increased in HCC and promotes HCC cell growth, proliferation and migration.

Deficiency of Carbamoyl Phosphate Synthetase 1 Engenders Radioresistance in Hepatocellular Carcinoma via Deubiquitinating c-Myc.

Purpose: Tumor radiation resistance is the main obstacle to effective radiation therapy for patients with hepatocellular carcinoma (HCC). We identified the role of urea cycle key enzyme carbamoyl phosphate synthetase 1 (CPS1) in radioresistance of HCC and explored its mechanism, aiming to provide a novel radiosensitization strategy for the CPS1-deficiency HCC subtype.

Methods And Materials: The expression of CPS1 was measured by western blot and immunohistochemistry.

Prediction of response and adverse drug reaction of pemetrexed plus platinum-based chemotherapy in lung adenocarcinoma by serum metabolomic profiling.

Background: Pemetrexed plus platinum doublet chemotherapy regimen remains to be the standard first-line treatment for lung adenocarcinoma patients. However, few biomarkers can be used to identify potential beneficiaries with maximal efficacy and minimal toxicity. This study aimed to explore potential biomarker models predictive of efficacy and toxicity after pemetrexed plus platinum chemotherapy based on metabolomics profiling.

Arginine methyltransferase PRMT5 methylates and destabilizes Mxi1 to confer radioresistance in non-small cell lung cancer.

Radioresistance is regarded as the main cause of local recurrence and distant metastasis in non-small cell lung cancer. However, the underlying mechanisms of radioresistance remains incompletely understood. In this study, we find that the arginine methyltransferase PRMT5 interacts with and methylates Mxi1, which promotes the binding of the β-Trcp ligase to Mxi1, facilitating the ubiquitination and degradation of Mxi1 in lung cancer.

Targeting KDM4C enhances CD8 T cell mediated antitumor immunity by activating chemokine CXCL10 transcription in lung cancer.

Background: Although immune checkpoint blockade (ICB) has been proven to achieve a persistent therapeutic response in various tumor types, only 20%-40% of patients benefit from this treatment. Radiotherapy (RT) can enhance tumor immunogenicity and improve the ICB response, but the outcome achieved by combining these two modalities remains clinically unsatisfactory. We previously uncovered that lysine-specific demethylase 4C (KDM4C) is a regulator of radiosensitivity in lung cancer.

BRD4-IRF1 axis regulates chemoradiotherapy-induced PD-L1 expression and immune evasion in non-small cell lung cancer.

Background: Chemoradiotherapy-induced PD-L1 upregulation leads to therapeutic resistance and treatment failure. The PD-1/PD-L1 blocking antibodies sensitize cancers to chemoradiotherapy by blocking extracellular PD-1 and PD-L1 binding without affecting the oncogenic function of intracellular PD-L1. Reversing the chemoradiation-induced PD-L1 expression could provide a new strategy to achieve a greater anti-tumour effect of chemoradiotherapy.

Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis.

Cancer cell radioresistance is the primary cause of the decreased curability of non-small cell lung cancer (NSCLC) observed in patients receiving definitive radiotherapy (RT). Following RT, a set of microenvironmental stress responses is triggered, including cell senescence. However, cell senescence is often ignored in designing effective strategies to resolve cancer cell radioresistance.

Precise pathological classification of non-small cell lung adenocarcinoma and squamous carcinoma based on an integrated platform of targeted metabolome and lipidome.

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are the most common subtypes of NSCLC. Despite genetic differences between LUAD and LUSC have been clarified in depth, the metabolic differences of these two subtypes are still unclear.

Benefit from Adjuvant TKIs Versus TKIs Plus Chemotherapy in -Mutant Stage III-pN2 Lung Adenocarcinoma.

Background: Recent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor ()-mutant stage III-pN2 lung adenocarcinoma.

Methods: Two hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated.

USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription.

Radioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients.

β-Trcp and CK1δ-mediated degradation of LZTS2 activates PI3K/AKT signaling to drive tumorigenesis and metastasis in hepatocellular carcinoma.

Distant metastasis is the leading cause of treatment failure in patients with hepatocellular carcinoma (HCC). However, the underlying mechanisms have not been fully elucidated. Here, we report that Leucine zipper tumor suppressor 2 (LZTS2) is downregulated and correlated with poor prognosis in HCC.

Cyclin K interacts with β-catenin to induce Cyclin D1 expression and facilitates tumorigenesis and radioresistance in lung cancer.

Radioresistance remains the major cause of local relapse and distant metastasis in lung cancer. However, the underlying molecular mechanisms remain poorly defined. This study aimed to investigate the role and regulatory mechanism of Cyclin K in lung cancer radioresistance.

Risk Prediction for Locoregional Recurrence in Epidermal Growth Factor Receptor-Mutant Stage III-pN2 Lung Adenocarcinoma after Complete Resection: A Multi-center Retrospective Study.

This study aimed to develop a predictive model based on the risk of locoregional recurrence (LRR) in epidermal growth factor receptor ()-mutant stage III-pN2 lung adenocarcinoma after complete resection. A total of 11,020 patients with lung surgery were screened to determine completely resected -mutant stage III-pN2 lung adenocarcinoma. Patients were excluded if they received preoperative therapy or postoperative radiation therapy (PORT).

Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer.

Background: NEK2, a serine/threonine kinase involved in mitosis, has been found to function in chromosome instability, tumor progression and metastasis, but its role in cervical cancer radioresistance remains unknown.

Methods: We detected the protein levels of NEK2 in cervical carcinoma tissues and paired paracarcinoma tissues by immunohistochemistry. The roles of NEK2 in oncogenesis were examined using cell growth and colony formation assays, EdU assay, apoptosis assay as well as in vivo mouse model.

UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance.

UBE2O, an E2/E3 hybrid ubiquitin-protein ligase, has been implicated in the regulation of adipogenesis, erythroid differentiation, and tumor proliferation. However, its role in cancer radioresistance remains completely unknown. Here, we uncover that UBE2O interacts and targets Mxi1 for ubiquitination and degradation at the K46 residue.

IQGAP3 interacts with Rad17 to recruit the Mre11-Rad50-Nbs1 complex and contributes to radioresistance in lung cancer.

IQ motif containing GTPase-activating protein 3 (IQGAP3) has been implicated in diverse cellular processes, including neuronal morphogenesis, cell proliferation and motility, and epithelial-mesenchymal transition. However, its role in cancer radioresistance is completely unknown. Here, we report that IQGAP3 is overproduced in lung cancer patients and correlates with poor clinical outcomes.

CDK7 inhibitor THZ1 enhances antiPD-1 therapy efficacy via the p38α/MYC/PD-L1 signaling in non-small cell lung cancer.

Background: The cyclin-dependent kinase 7 (CDK7) subunit of TFIIH regulates RNA polymerase-II-based transcription and promotes tumor progression. However, the mechanisms involved in CDK7-mediated immune evasion are unclear in non-small cell lung cancer (NSCLC).

Methods: RNA silencing and pharmacologic inhibitors were used to evaluate the functions of CDK7/p38α/MYC/PD-L1 axis in cancer cell proliferation and antiPD-1 therapy resistance.

CDK5 Activates Hippo Signaling to Confer Resistance to Radiation Therapy Via Upregulating TAZ in Lung Cancer.

Purpose: Tumor resistance to radiation therapy is a therapeutic challenge in the treatment of patients with non-small cell lung cancer. Cyclin-dependent kinase 5 (CDK5) has been proposed to participate in cell proliferation, migration and invasion, drug resistance, and immune evasion. However, the functions and regulatory mechanisms of CDK5 in lung cancer radioresistance have not been investigated.

Downregulation of ABI2 expression by EBV-miR-BART13-3p induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells through upregulation of c-JUN/SLUG signaling.

Existing evidence has shown that circulating Epstein-Barr virus (EBV)-miR-BART13-3p is highly expressed in plasma of nasopharyngeal carcinoma (NPC) patients, especially among patients with advanced diseases. However, the exact role that EBV-miR-BART13-3p plays in the development of NPC remains poorly understood. Here we show that up-regulated expression of EBV-miR-BART13-3p leads to increased capacity in migration and invasion of NPC cells and causes tumor metastasis .