circFTO from M2 macrophage-derived small extracellular vesicles (sEV) enhances NSCLC malignancy by regulation miR-148a-3pPDK4 axis.

BACKGROUND: Accumulation studies found that tumor-associated macrophages (TAMs) are a predominant cell in tumor microenvironment (TME), which function essentially during tumor progression. By releasing bioactive molecules, including circRNA, small extracellular vesicles (sEV) modulate immune cell functions in the TME, thereby affecting non-small cell lung cancer (NSCLC) progression. Nevertheless, biology functions and molecular mechanisms of M2 macrophage-derived sEV circRNAs in NSCLC are unclear. METHODS: Cellular experiments were conducted to verify the M2 macrophage-derived sEV (M2-EV) roles in NSCLC. Differential circRNA expression in M0 and M2-EV was validated by RNA sequencing. circFTO expression in NSCLC patients and cells was investigated via real-time PCR and FISH. The biological mechanism of circFTO in NSCLC was validated by experiments. Our team isolated sEV from M2 macrophages (M2Ms) and found that M2-EV treatment promoted NSCLC CP, migration, and glycolysis. RESULTS: High-throughput sequencing found that circFTO was highly enriched in M2-EV. FISH and RT-qPCR confirmed that circFTO expression incremented in NSCLC tissues and cell lines. Clinical studies confirmed that high circFTO expression correlated negatively with NSCLC patient survival. Luciferase reporter analysis confirmed that miR-148a-3p and PDK4 were downstream targets of circFTO. circFTO knockdown inhibited NSCLC cell growth and metastasis in in vivo experiments. Downregulating miR-148a-3p or overexpressing PDK4 restored the malignancy of NSCLC, including proliferation, migration, and aerobic glycolysis after circFTO silencing. CONCLUSION: The study found that circFTO from M2-EV promoted NSCLC cell progression and glycolysis through miR-148a-3p/PDK4 axis. circFTO is a promising prognostic and diagnostic NSCLC biomarker and has the potential to be a candidate NSCLC therapy target.

Stacking Transformation-Triggered Circularly Polarized Luminescence Reversion in γ-Cyclodextrins-Pyrene Co-assembly.

​Considerable attention has been directed towards cyclodextrins (CDs) in the creation of co-assembled CPL-active materials, owing to their intrinsic chiral host cavities and synergistic host-guest interactions. However, achieving reversed CPL emission regulation with single-handedness CDs moiety poses a significant challenge. In this study, we have devised a series of γ-CD-based host-guest complexes comprising dual pyrene imidazolium derivatives with multiple linkers, which exhibit reversed circularly polarized emission. We have uncovered that the transformation of excimer stacking within γ-CD/pyrene complexes contributes to the inverted CPL emissions originating from a single-handed chiral host. This research elucidates the phenomenom of (+)- and (-)-circularly polarized excimer emission (CPEE) within γ-CD, arising from right- and left-handed stacking conformations, respectively.

The abnormal expression of circ-ARAP2 promotes ESCC progression through regulating miR-761/FOXM1 axis-mediated stemness and the endothelial-mesenchymal transition.

Circular RNAs (circRNAs) belong to a novel class of noncoding RNA that gained more attention in human cancer pathogenesis. The role of circRNA in esophageal squamous cell carcinoma (ESCC) is largely unclear. Present investigation was to characterize new circRNAs regulating ESCC progression and explore the regulatory mechanisms in ESCC. In this study, circRNAs differentially expressed in ESCC and adjacent normal tissues were characterized via high-throughput sequencing. Then the differentially expressed circRNA between ESCC and adjacent normal tissues were investigated using Rt-qPCR. The role of circ-ARAP2 expression on tumor progression were detected in both in vivo and in vitro. Luciferase reporter assays were used to identify the relationships among circ-ARAP2, microRNA (miR)-761 and the cell cycle regulator Forkhead Box M1 (FOXM1). The result of the expression profile analyses regarding human circRNAs in ESCC demonstrated that circ-ARAP2 was up-regulated significantly in both ESCC tissues and cell lines. Downregulation circ-ARAP2 suppressed ESCC proliferation, tumor growth and metastasis in both in vivo and in vitro. The data also suggested that miR-761 and FOXM1 were circ-ARAP2 downstream targets which were confirmed through luciferase reporter analysis. Overexpression of FOXM1 or inhibiting miR-761 restored ESCC cell proliferation and invasion ability after silencing circ-ARAP2. The study also found that circ-ARAP2 influenced the endothelial-mesenchymal transition (EMT) and cancer stem cells differently by regulating miR-761/FOXM1. In one word, the results demonstrated that abnormal circ-ARAP2 expression promoted ESCC progression by regulating miR-761/FOXM1 axis-mediated stemness and EMT.

ARHGAP24 inhibits cell proliferation and cell cycle progression and induces apoptosis of lung cancer via a STAT6-WWP2-p27 axis.

Rho GTPase-activating proteins (RhoGAPs) have been reported to be of great importance in the initiation and development of many different cancers. However, their biological roles and regulatory mechanisms in lung cancer development and progression are poorly defined. Real-time PCR or western blotting analysis was used to detect Rho GTPase-activating protein 24 (ARHGAP24), WWP2, p27, p-STAT6 and STAT6 expression levels as well as the activity of RhoA and Rac1 in lung cancer. Cell proliferation, apoptosis and cell cycle were measured by CCK-8 and flow cytometry analysis. Tumor growth of lung cancer cells was measured using a nude mouse xenograft experiment model in vivo. The correlation between WWP2 and p27 was measured by co-immunoprecipitation and ubiquitination analysis. We found that ARHGAP24 expression was lower in lung cancer tissues collected from the The Cancer Genome Atlas and independent hospital database. Overexpression of ARHGAP24 significantly suppressed cell proliferation and the activity of RhoA and Rac1, induced cell apoptosis and arrested cell cycle at the G0-G1 phase. ARHGAP24 overexpression also inhibited tumor growth in nude mice, whereas knockdown of ARHGAP24 significantly promoted cell proliferation and WWP2 expression and inhibited cell cycle arrest at G1 phase through activating STAT6 signaling. ARHGAP24 overexpression inhibited WWP2 overexpression-induced cell proliferation, cell cycle progression and the decreased p27 expression. Moreover, WWP2 was found interacted with p27, and WWP2 overexpression promoted the ubiquitination of p27. In conclusion, our findings suggest that ARHGAP24 inhibits cell proliferation and cell cycle progression and induces cell apoptosis of lung cancer via a STAT6-WWP2-p27 axis.

Rho GTPase Activating Protein 24 (ARHGAP24) Silencing Promotes Lung Cancer Cell Migration and Invasion by Activating ß-Catenin Signaling.

BACKGROUND Rho GTPase activating protein (RhoGAPs) is an important negative regulator of the Rho signaling pathway that is involved in tumorigenesis in liver, colon, and renal cancer. However, the mechanism by which Rho GTPase activating protein 24 (ARHGAP24) regulates cell invasion and migration of lung cancer has not been fully explained. MATERIAL AND METHODS In this study, ARHGAP24 expression in lung cancer tissues and cell lines was measured by immunohistochemical and Western blot analysis. Transwell or wound healing analysis was performed to detect the cell migration and invasion of ARHGAP24 modulated A549 and NCI-H1975 cells with ß-catenin inhibitor XAV-939 (10 µM) treatment, and the expression of MMP9, VEGF, and ß-catenin protein was measured by Western blotting. RESULTS Our results showed that ARHGAP24 expression was downregulated in lung cancer tissues and cell lines. pLVX-Puro-ARHGAP24 transfection in A549 cells significantly inhibited cell invasion and migration, along with increased E-cadherin and decreased MMP9, VEGF, Vimentin, and ß-catenin protein expression. pLKO.1-ARHGAP24-shRNA transfection in NCI-H1975 cells significantly promoted cell invasion and migration, accompanied with decreased E-cadherin and increased MMP9, VEGF, and ß-catenin protein expression. Moreover, NCI-H1975 cells with XAV-939 treatment showed decreased cell invasion and migration when compared with pLKO.1-ARHGAP24-shRNA transfection. ARHGAP24 silencing promoted the transcriptional activity of ß-catenin in NCI-H1975 cells. CONCLUSIONS Our findings indicate that ARHGAP24 silencing promotes lung cancer cell migration and invasion through activating ß-catenin signaling.

Marine-derived protein kinase inhibitors for neuroinflammatory diseases.

Neuroinflammation is primarily characterized by overexpression of proinflammatory mediators produced by glial activation or immune cell infiltration. Several kinases have been shown to be critical mediators in neuroinflammation. One of the largest groups of kinases is protein kinases, which have been the second most studied group of drug targets after G-protein-coupled receptors. Thus far, most of the approved kinase inhibitor drugs are adenosine triphosphate-competitive inhibitors with various off-target liabilities because of cross-reactivities; however, marine-derived compounds provide opportunities for discovering allosteric kinase inhibitors. This review summarizes the potential of marine-derived protein kinase inhibitors in the field of neuroinflammatory diseases, such as Parkinson disease, Alzheimer disease, multiple sclerosis, and pain. The previous studies from 1990 to 2017 in this review have shown that marine-derived protein kinase inhibitors have great potential to elicit anti-neuroinflammatory or neuroprotective responses in in vitro and in vivo models of neuroinflammatory diseases. This suggests that further exploration and investigation of these marine-derived protein kinase inhibitors on neuroinflammatory diseases are warranted. Therefore, this review may inspire further discovery of new protein kinase inhibitors from a marine origin and additional neuroscience studies focusing on these valuable marine-derived protein kinase inhibitors.

Activated cdc42-associated kinase is up-regulated in non-small-cell lung cancer and necessary for FGFR-mediated AKT activation.

Activated cdc42-associated tyrosine kinase 1 (ACK1) has been reported to be implicated in non-small-cell lung cancer (NSCLC). However, the expression pattern and biological functions of ACK1 in the progression of NSCLC are not fully understood. In this study, it was found that the expression of ACK1 was significantly up-regulated in NSCLC samples compared to their adjacent normal tissues. Meanwhile, the expression of ACK1 was inversely correlated with the survival of NSCLC patients. Moreover, in the biological function studies, ACK1 was further validated to promote the growth, migration, and metastasis of NSCLC cells in vitro and in vivo. Mechanistically, ACK1 bind with FGFR1 and was essential for the phosphorylation of AKT induced by FGF. Our study demonstrated that ACK1 played an oncogenic role in the progression of NSCLC and ACK1 might be a promising target for the treatment of NSCLC.

TMEM45B, up-regulated in human lung cancer, enhances tumorigenicity of lung cancer cells.

Transmembrane protein 45B (TMEM45B) is a member of TMEMs. Altered expression of TMEMs is frequently observed in a variety of human cancers, but the expression and functional roles of TMEM45B in lung cancer is not reported. In the present study, levels of mRNA expression of TMEM45B in lung cancer tissues were assessed using re-analyzing expression data of The Cancer Genome Atlas (TCGA) lung cancer cohort and real-time PCR analysis on our own cohort. Lung cancer cells, A549 and NCI-H1975, infected with TMEM45B short hairpin RNA were examined in cell proliferation, cell cycle, cell apoptosis, wound-healing, and cell invasion assays as well as mouse xenograft models. Here, we demonstrated that TMEM45B was overexpressed in lung cancer and its expression correlated with overall survival of patients. In addition, silencing of TMEM45B expression reduced cell proliferation in vitro and in vivo, induced cell cycle arrest and cell apoptosis, and blocked cell migration and invasion. Moreover, knockdown of TMEM45B significantly suppressed G1/S transition, induced cell apoptosis, and inhibited cell invasion via regulating the expression of cell cycle-related proteins (CDK2, CDC25A, and PCNA), cell apoptosis-related proteins (Bcl2, Bax, and Cleaved Caspase 3), and metastasis-related proteins (MMP-9, Twist, and Snail), respectively. Thus, TMEM45B is a potential prognostic marker and cancer-selective therapeutic target in lung cancer.

Expression and characterization of bifunctional fusion proteins possessing antitumor and thrombolytic function for targeting therapy.

It is a usual clinical phenomenon that cancer patients are prone to thrombosis. Until now, there have been no efficient methods or appropriate drugs to prevent and cure tumor thrombus. ΔSEC2, N-terminal deletion of 17 amino acids and C-terminal deletion of 132 amino acids, retained antitumor activity of SEC2. ΔSak, N-terminal deletion of 10 amino acids, had thrombolytic activity and specificity advantages. By utilizing bioactivities of ΔSEC2 and ΔSak, ΔSEC2-ΔSak and ΔSak-ΔSEC2 were constructed. Octreotide is a tumor targeting peptide and it can be combined with somatostatin (SST) receptors of tumor surface in ligand-receptor binding way. It can be used to increase specificity for tumor therapy. Based on previous studies, DNA sequence encoding octreotide gene was inserted into plasmid pET-28a-Δsec2-Δsak and pET-28a-Δsak-Δsec2. After expression and purification, fusion proteins could significantly stimulate proliferation of mouse spleen lymphocyte, obviously inhibit the growth of human gastric carcinoma BGC-823, and have thrombolytic activity, indicating that fusion proteins retained bioactivities of staphylococcal enterotoxin C2 and Sak. Furthermore, tumor binding capacity of fusion protein was confirmed through the coimmunoprecipitation method. The result showed that they could bind SST receptor 2 antibody, indicating that fusion proteins could be specifically targeted to tumor surface. It has important significance and may be used for targeted therapy.

Pyruvate kinase M2 interacts with DNA damage-binding protein 2 and reduces cell survival upon UV irradiation.

Pyruvate Kinase M2 (PKM2) is highly expressed in many solid tumors and associated with metabolism reprogramming and proliferation of tumors. Here, we report that PKM2 can bind to DNA Damage-Binding Protein 2 (DDB2), which is necessary for global nucleotide excision repair of UV induced DNA damage. The binding is promoted by UV irradiation and K433 acetylation of PKM2. Over expression of PKM2 facilitates phosphorylation of DDB2 and impairs DDB2-DDB1 binding. Furthermore, knocking down of PKM2 increases cell survival upon UV irradiation, while over expression of PKM2 reduces cell survival and over expression of DDB2-DDB1 reverts this effect. These results reveal a previously unknown regulation of PKM2 on DDB2 and provide a possible mechanism for UV induced tumorigenesis.

USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer.

The histone ubiquitin hydrolase ubiquitin-specific protease 22 (USP22) is an epigenetic modifier and an oncogene that is upregulated in many types of cancer. In non-small cell lung cancer (NSCLC), aberrant expression of USP22 is a predictor of poor survival, as is high expression of cyclooxygenase-2 (COX-2). Despite its oncogenic role, few substrates of USP22 have been identified and its mechanism of action in cancer remains unclear. Here, we identified COX-2 as a direct substrate of USP22 and showed that its levels are modulated by USP22 mediated deubiquitination. Silencing of USP22 downregulated COX-2, decreased its half-life, and inhibited lung carcinoma cell proliferation by directly interacting with and modulating the stability and activity of COX-2 through the regulation of its ubiquitination status. The findings of the present study suggest a potential mechanism underlying the oncogenic role of USP22 mediated by the modulation of the stability and activity of COX-2.

miR-342-3p targets RAP2B to suppress proliferation and invasion of non-small cell lung cancer cells.

MicroRNAs (miRNAs) play critical roles in cancer development and progression. In this study, we examined the roles and molecular mechanisms of miR-342-3p in human non-small cell lung cancer (NSCLC). The results showed that miR-342-3p is downregulated in NSCLC cell lines and tissues, and its overexpression induces significant inhibition of NSCLC cell proliferation, invasion, and tumor growth in nude mice. In addition, miR-342-3p repressed RAP2B expression through interactions with its 3'-UTR region. Restoration of RAP2B expression reversed miR-342-3p-mediated inhibitory activity in NSCLC cells. Finally, analyses of miR-342-3p and RAP2B levels in NSCLCs revealed that miR-342-3p inversely correlated with RAP2B mRNA expression. Our collective findings provide preliminary evidence that miR-342-3p acts as a tumor suppressor in NSCLC through repression of RAP2B.

[PFKFB3 regulates 11'-deoxyverticillin A (C42)-induced autophagy and apoptosis in HeLa cells].

OBJECTIVE: The aim is to reveal the role of PFKFB3 in 11'-deoxyverticillin A (C42)-induced autophagy and apoptosis. METHODS: Electron and fluorescence microscopy, immunoblotting, MTS assay, siRNA interference and real time PCR were used. RESULTS: C42 could induce multiple cell death in HeLa cells. Knockdown of either Beclin 1 or LC3, two important autophagic genes, increased both PARP-1 cleavage and cell viability loss. Although high dose of C42 triggered more cell viability loss, yet, it failed to augment autophagic flux. While PFKFB3 inhibitors attenuated C42-induced autophagy, the overexpression of PFKFB3 increased the induced autophagic flux. CONCLUSION: PFKFB3 is involved in C42 induced-autophagy, which blunts the caspase-dependent apoptotic process.

Down-regulation of EphB4 phosphorylation is necessary for esophageal squamous cell carcinoma tumorigenecity.

Eph/ephrin signaling system plays a very important role in the tumorigenesis and the formation of blood vessel. However, the function of EphB4 and its ligand ephrin B2 in the carcinogenesis of esophageal squamous cell carcinoma (ESCC) is not fully understood. Here, it was found that the expression of EphB4 was up-regulated in ESCC tissues compared with the paired normal tissues, while ephrin B2 was down-regulated in ESCC samples. Phosphorylation of EphB4 induced by its ligand ephrin B2-Fc inhibited the growth, migration and colony formation of ESCC cells. Moreover, over-expression of EphB4 or EphB4 kinase dead mutant (EphB4 KD) in ESCC cells promoted cell growth and migration, suggesting EphB4 promoted cell growth and migration independent of its kinase activity. Furthermore, we found that EphB4 interacted with the adaptor protein RACK1 and RACK1 decreased the phosphorylation level of EphB4. Taken together, our study revealed the important function and regulation of EphB4 in the progression of ESCC and suggested EphB4 as a novel target for the treatment of ESCC.

Construction of novel chimeric proteins through the truncation of SEC2 and Sak from Staphylococcus aureus.

It is an usual clinical phenomenon that cancer patients are prone to thrombosis. Until now, there have been no efficient methods or appropriate drugs to prevent and cure tumor thrombus. Therefore, the construction of a bifunctional chimeric protein for the treatment of cancer, complicated with thrombosis, is of great significance. Utilizing the superantigenic activity of staphylococcal enterotoxin C2 (SEC2) and the thrombolytic activity of staphylokinase (Sak), Sak-linker-SEC2 and SEC2-linker-Sak were constructed which had good anti-tumor and thrombolytic activities at the same time. Due to the intrinsic emetic activity of SEC2 and high molecular weight (MW) of chimeric proteins (44 kDa), their clinical applications will be restricted. In this study, novel chimeric proteins including ΔSEC2-ΔSak and ΔSak-ΔSEC2 were constructed through the truncation of SEC2 and Sak without 9-Ala linker and His-tag. Compared with the former, both the truncated proteins preserved nearly the same anti-tumor and thrombolytic activities. In addition, their MWs were only 29 kDa and their immunoreactivities were slightly lower than that of Sak-linker-SEC2 and SEC2-linker-Sak, respectively. Therefore, the novel chimeric proteins possessed merits and characteristics, such as low MS, low immunogenicity, and difunctionality which the former had not. It will be of great interest if the above-mentioned proteins can be used to cure Trousseau syndrome in clinic.

USP22 promotes NSCLC tumorigenesis via MDMX up-regulation and subsequent p53 inhibition.

Increasing evidence suggests that ubiquitin-specific protease 22 (USP22) has great clinicopathologic significance in oncology. In this study, we investigated the role of USP22 in human NSCLC tumorigenesis along with the underlying mechanisms of action. First, we determined the expression of USP22 in human NSCLC, as well as normal tissues and cell lines. We then studied the effects of USP22 silencing by shRNA on NSCLC cell growth in vitro and tumorigenesis in vivo, along with the effect on the p53 pathway. We found that USP22 is overexpressed in human NSCLC tissues and cell lines. USP22 silencing by shRNA inhibits proliferation, induces apoptosis and arrests cells at the G0/G1 phases in NSCLC cells and curbs human NSCLC tumor growth in a mouse xenograft model. Additionally, USP22 silencing downregulates MDMX protein expression and activates the p53 pathway. Our co-immunoprecipitation analysis shows that USP22 interacts with MDMX in NSCLC cells. Furthermore, MDMX silencing leads to growth arrest and apoptosis in NSCLC cells, and over-expression of MDMX reverses the USP22 silencing-induced effects. Taken together, our results suggest that USP22 promotes NSCLC tumorigenesis in vitro and in vivo through MDMX upregulation and subsequent p53 inhibition. USP22 may represent a novel target for NSCLC treatment.

Characterisation and comparison of enzymatically prepared donkey milk whey protein hydrolysates.

This study evaluated the structural characteristics, processing properties, and antioxidant properties of hydrolysates prepared from donkey milk (DM) whey protein using different proteases (Alcalase, Neutrase, papain, and Flavourzyme). The results showed that enzymatic hydrolysis significantly increased hydrolysate solubility and reduced average particle size compared to those of DM whey protein. Neutrase and Flavourzyme hydrolysates exhibited higher degrees of hydrolysis (DH), along with elevated emulsification properties and surface hydrophobicity. The choice of protease influenced secondary and tertiary protein structures and amino acid composition. Enzymatic hydrolysis led to decreased molecular weight of DM whey proteins. Moreover, all hydrolysates exhibited higher fluorescence intensity at λmax compared to DM whey protein, implying distinct properties due to the varied impacts of the four proteases on DM whey protein structure. The preparation of hydrolysates from DM whey proteins using proteases contributes to the development of integrated-value DM products.

Raman spectroscopy for esophageal tumor diagnosis and delineation using machine learning and the portable Raman spectrometer.

Esophageal cancer is one of the leading causes of cancer-related deaths worldwide. The identification of residual tumor tissues in the surgical margin of esophageal cancer is essential for the treatment and prognosis of cancer patients. But the current diagnostic methods, either pathological frozen section or paraffin section examination, are laborious, time-consuming, and inconvenient. Raman spectroscopy is a label-free and non-invasive analytical technique that provides molecular information with high specificity. Here, we report the use of a portable Raman system and machine learning algorithms to achieve accurate diagnosis of esophageal tumor tissue in surgically resected specimens. We tested five machine learning-based classification methods, including k-Nearest Neighbors, Adaptive Boosting, Random Forest, Principal Component Analysis-Linear Discriminant Analysis, and Support Vector Machine (SVM). Among them, SVM shows the highest accuracy (88.61 %) in classifying the esophageal tumor and normal tissues. The portable Raman system demonstrates robust measurements with an acceptable focal plane shift of up to 3 mm, which enables large-area Raman mapping on resected tissues. Based on this, we finally achieve successful Raman visualization of tumor boundaries on surgical margin specimens, and the Raman measurement time is less than 5 min. This work provides a robust, convenient, accurate, and cost-effective tool for the diagnosis of esophageal cancer tumors, advancing toward Raman-based clinical intraoperative applications.

RACK1 promoted the growth and migration of the cancer cells in the progression of esophageal squamous cell carcinoma.

Dysregulation of hedgehog signaling has been involved in esophageal squamous cell carcinoma (ESCC) by the mechanisms that are not fully understood. The receptor for activated protein kinase C (RACK1) is involved in the progression of multiple cancers. However, its expression and function in ESCC have not been investigated. Here, we found that the expression of RACK1 was upregulated in ESCC clinical samples. Moreover, over-expression of RACK1 in ESCC cells promoted cell proliferation and migration, while downregulation of RACK1 impaired the proliferation and migration of ESCC cells in vitro and in vivo. Mechanistically, RACK1 promoted the proliferation and migration of ESCC cells by activating hedgehog signaling. Taken together, our study suggested RACK1 might be an important therapeutic target in ESCC.

Depleting DDX1 sensitizes non-small cell lung cancer cells to chemotherapy by attenuating cancer stem cell traits.

AIMS: DEAD-box helicase 1 (DDX1) has oncogenic properties in several human cancers. However, the clinical significance and biological role of DDX1 in non-small cell lung cancer (NSCLC) remain elusive. Here, we examined the chemotherapeutic relevance of DDX1 in NSCLC. MAIN METHODS: We used the UALCAN database, Western blot analysis, and immunohistochemical and RT-qPCR assays to assess DDX1 expression in NSCLC cell lines (H1650 and A549) and patient tissues. The role of DDX1 in the chemosensitivity of NSCLC cells and the underlying mechanisms were determined using colony formation, CCK-8, flow cytometry, wound healing, Transwell, tumor sphere formation, and immunostaining assays, together with a xenograft tumor model in nude mice. KEY FINDINGS: Our study revealed that DDX1 was overexpressed in NSCLC cell lines and tissues. We further found that depleting DDX1 increased the sensitivity of NSCLC cells to the chemotherapy drug cisplatin, increased cell apoptosis, and inhibited cell migration and invasion. Co-immunoprecipitation assays revealed that DDX1 bound to ADAR1, and increased ADAR1 protein expression. Furthermore, we found that ADAR1 mediated cancer-promoting effects, independent of deaminase activity, by binding to RAC3 mRNA. Our findings not only show that DDX1 mediates chemosensitivity to cisplatin via the ADAR1/RAC3 axis but also highlight the importance of ADARs as essential RNA-binding proteins for cell homeostasis, as well as cancer progression. SIGNIFICANCE: Our results suggest that DDX1 plays an important role in the development and progression of human NSCLC and that DDX1 may serve as a therapeutic target in NSCLC patients.