Expression In Lung Cancer Tissues Research Articles

Mogrol-Mediated enhancement of radiotherapy sensitivity in Non-Small cell lung cancer: A mechanistic study.

Investigate Mogrol's impact on NSCLC radiosensitivity and underlying mechanisms using various methods including assays, bioinformatics, and xenograft models. CCK-8, clonogenic, flow cytometry, TUNEL, and Western blot assays evaluated Mogrol and radiation effects on NSCLC viability and apoptosis. USP22 expression in NSCLC patient tissues was determined using RT-qPCR and Western blot. A xenograft model validated Mogrol's effects on tumor growth. Bioinformatics identified four ubiquitin-specific proteases, including USP22, in NSCLC. Kaplan-Meier analysis confirmed USP22's value in lung cancer survival. HPA database indicated higher USP22 expression in lung cancer tissues. GO and KEGG analysis implicated ERK1/2 in NSCLC progression, and molecular docking showed stability between Mogrol and ERK1/2. Further in vivo and in vitro experiments have demonstrated that Mogrol enhances the inhibitory effect of radiation on NSCLC cell viability and clonogenic capacity. Cell viability and clonogenic capacity are reduced by more than 50%, and an increase in cellular apoptosis is observed, with apoptotic levels reaching 10%. USP22 expression was significantly elevated in NSCLC tissues, particularly in radiotherapy-resistant patients. Mogrol downregulated USP22 expression by inhibiting the ERK/CREB pathway, lowering COX2 expression. Mogrol also enhanced radiation's inhibition of tumor growth in mice. Mogrol enhances NSCLC radiosensitivity by downregulating USP22 via the ERK/CREB pathway, leading to reduced COX2 expression.

High CASC expression predicts poor prognosis of lung cancer: A systematic review with meta-analysis.

The long non-coding RNA cancer susceptibility candidate (CASC) has abnormal expression in lung cancer tissues and may correlate with lung cancer prognosis. This study aimed to comprehensively evaluate the association between CASC expression and the cancer prognosis. PubMed, Embase, Web of Science, Google Scholar, Cochrane Library, and China National Knowledge Infrastructure databases were searched until April 1, 2023, to obtain the relevant literature. Studies that met the predefined eligibility criteria were included, and their quality was independently assessed by 2 investigators according to the Newcastle-Ottawa Scale (NOS) score. Detailed information was obtained, such as first author, year of publication, and number of patients. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted and grouped to assess the relationship between CASC expression and cancer prognosis. The dichotomous data was merged and shown as the odds ratio (OR) with a 95% CI was extracted to assess the relationship between CASC expression and clinicopathological parameters. A total of 12 studies with 746 patients with lung cancer were included in the meta-analysis. The expression levels of lncRNA CASC2 and CASC7 were decreased, while those of CASC9, 11, 15, and 19 were induced in lung cancer tissues compared with paracancerous tissues. In the population with low CASC expression (CASC2 and CASC7), high CASC expression indicated a good lung cancer prognosis (HR = 0.469; 95% CI, 0.271-0.668). Conversely, in the population with high CASC expression (CASC9, 11, 15, and 19), high CASC expression predicted a poor lung cancer outcome (HR = 1.910; 95% CI, 1.628-2.192). High CASC expression also predicted worse disease-free survival (DFS) (HR = 2.803; 95% CI, 1.804-6.319). Combined OR with 95% CI revealed an insignificant positive association between high CASC expression and advanced TNM stage (OR = 1.061; 95% CI, 0.775-1.454), LNM (OR = 0.962; 95% CI, 0.724-1.277), tumor size (OR = 0.942; 95% CI, 0.667-1.330), and histological grade (OR = 1.022; 95% CI, 0.689-1.517). The CASC expression levels negatively correlate with lung cancer prognosis. Therefore, CASC expression may serve as a prognostic marker and a potential therapeutic target for lung cancer.

Linc00958 Promotes Lung Cancer Proliferation and Migration Through Regulating microRNA-490-3p

This study aimed to investigate the role of long intergenic non-protein coding RNA 00958 (Linc00958) in lung cancer (LCa) progression and its underlying mechanism. The study assessed Linc00958 expression in LCa tissues and adjacent tissues using qRT-PCR, and its impact on patient prognosis was analyzed through Kaplan-Meier survival analysis. Additionally, Linc00958 expression in LCa and normal lung cell lines was examined in vitro. Functional assays, including CCK-8, EdU, and transwell assays, were conducted to evaluate the effects of Linc00958 knockdown on LCa cells. To uncover the molecular mechanism, a dual-luciferase reporter assay was used to confirm the binding relationship between Linc00958 and microRNA-490-3p, a downstream gene. Co-transfection experiments were performed to elucidate microRNA-490-3p’s role in Linc00958’s impact on LCa cell functions. The results showed that Linc00958 was overexpressed in LCa tissues and cells, and high Linc00958 expression correlated with reduced patient survival. in vitro experiments revealed that Linc00958 promoted tumor proliferation and migration in LCa cells. Both computational predictions and dual-luciferase reporter assays demonstrated binding sites between microRNA-490-3p and Linc00958. Co-transfection experiments confirmed that Linc00958 facilitated LCa cell proliferation and migration through modulating microRNA-490-3p expression. In summary, Linc00958 promotes LCa cell proliferation and migration by regulating microRNA-490-3p.

GATA6 inhibits the biological function of non-small cell lung cancer by modulating glucose metabolism

PurposeThis study aims to explore the role of GATA6 in lung cancer, with a focus on its impact on metabolic processes.MethodsWe assessed GATA6 expression in lung cancer tissues and its association with patient prognosis. In vitro cell function experiments were conducted to investigate the effects of altered GATA6 levels on lung cancer cell proliferation and migration. Mechanistic insights were gained by examining GATA6's influence on glucose metabolism-related genes, particularly its effect on c-Myc mRNA expression.ResultsOur study revealed significant down-regulation of GATA6 in lung cancer tissues, and this down-regulation was strongly correlated with unfavorable patient prognosis. Elevating GATA6 levels effectively inhibited the proliferation and migration of lung cancer cells in our cell function experiments. Mechanistically, we found that GATA6 suppressed the expression of c-Myc mRNA, impacting genes related to glucose metabolism. As a result, glucose uptake and metabolism in lung cancer cells were disrupted, ultimately impeding their malignant behaviors.ConclusionOur study provides crucial insights into the metabolic regulation of GATA6 in lung cancer cells. These findings have the potential to offer a solid theoretical foundation for the development of novel clinical treatments for lung cancer.

Expression and prognosis analysis of TBX2 subfamily in human lung carcinoma.

Lung cancer has a high morbidity and mortality rate of all cancers worldwide. Therefore, there is an urgent need for reliable cancer markers for diagnosis and prognosis of patients with lung cancer. In this study, we used the bioinformatics database to compare the expression of the TBX2 subfamily at the transcriptional and protein levels in non-small cell lung cancer. Then, to confirm our bioinformatics analysis above, we used western bloting to determine the expression of TBX2, TBX3, TBX4 and TBX5 in human lung squamous carcinoma cell lines. Besides, low expression of TBX2 subfamily predicted a poor prognosis of patients with lung cancer. Finally, The methylation database was used to explore the relationship between the low expression of TBX2 subfamily and methylation of gene promoter region. Our data showed a significant decrease of TBX2 subfamily expression in lung cancer tissues of several histological subtypes. Finally, the methylation of TBX2 subfamily members in the promoter region of NSCLC was significantly higher than that in normal tissues. Our research provided sufficient evidence that TBX2 subfamily might play an inhibitory role in malignancy progression of lung cancer, which is promising to shed light on discovering a novel reliable cancer marker for prognosis of lung cancer patients.

NUF2 Expression in Cancer Tissues and Lymph Nodes Suggests Post-Surgery Recurrence of Non-Small Cell Lung Cancer.

In non-small cell lung cancer (NSCLC) cases, detecting potential lymph node metastases is essential to determine the indications for sublobar resection or adjuvant therapy. NUF2 is a tumor-specific antigen that is highly expressed in lung cancer tissues. However, the significance of analyzing NUF2 expression in dissected lymph nodes has not yet been studied. Thus, we investigated the association between NUF2 expression in lung cancer tissues and dissected lymph nodes and early recurrence of NSCLC to determine its usefulness as a marker of lymph node micrometastasis. This retrospective study quantified NUF2 expression in the cancer tissues of 88 patients with NSCLC who underwent complete resection using real-time polymerase chain reaction and investigated its relationship with clinicopathological features and prognosis. We also quantified NUF2 RNA expression in mediastinal lymph nodes from 255 patients with pN0 NSCLC who underwent complete resection with lymph node dissection and analyzed its association with prognosis. NUF2 expression in primary tumors was correlated with lymph node metastasis and unfavorable outcomes in terms of poor recurrence-free and cancer-specific survival. In N0 NSCLC cases, high NUF2 expression in mediastinal lymph nodes indicated poor prognosis, especially in lymph node recurrence. NUF2 emerges as a promising marker for predicting lymph node metastatic recurrence, offering potential utility in guiding post-surgical adjuvant therapy for lung cancer or assisting in intraoperative decisions for sublobar resection.

CMTM6: A Critical Prognostic Indicator in Non-Small Cell Lung Cancer.

While CKLF-like MARVEL transmembrane domain containing 6 (CMTM6)'s role in stabilizing PD-L1 and immune evasion within tumors is established, its expression in lung cancer tissue and adjacent macrophages remains uncertain. The study aimed to elucidate this ambiguity by investigating CMTM6's role in non-small cell lung cancer (NSCLC) prognosis. Employing immunohistochemical staining on 141 NSCLC and 110 adjacent normal lung tissue samples, CMTM6 expression was evaluated using the HSCORE system. Interestingly, NSCLC exhibited significantly higher CMTM6 levels (161.04±86.60) compared to normal tissues (71.20±45.10) (p < 0.001), detected not only in cancer cells but also in macrophages, lymphocytes, and nearby bronchial epithelial cells. Stratifying patients by CMTM6 levels unveiled a correlation between heightened expression and poorer overall survival (p = 0.003), alongside a link to tumor-infiltrating lymphocytes (TIL) (p = 0.037), especially in cases with increased TIL. Multivariate analysis identified CMTM6 as an independent predictor of overall survival (p = 0.009), implying that elevated CMTM6 expression in NSCLC might signify an adverse prognostic marker for patient outcomes.

SLC12A8 mediates TKI resistance in EGFR-mutant lung cancer via PDK1/AKT axis.

Epidermal growth factor receptor (EGFR) mutation is a prominent driver of lung cancer. Tyrosine kinase inhibitors (TKIs) have shown efficacy in treating EGFR-mutant lung cancer, but the emergence of drug resistance poses a significant challenge. Recent research has highlighted solute carrier family 12 member 8 (SLC12A8) as one of the highly upregulated genes in various cancer types. However, its oncogenic function remains largely unexplored. 343 consecutive lung cancer patients were prospectively recruited and were followed for over 10years. SLC12A8 expression in lung cancer tissues was measured by qPCR and was associated with patient survival. The association of SLC12A8 with TKI resistance was studied in in vitro EGFR-mutant lung cancer cell line as well as in in vivo xenograft tumor model. High-throughput kinome screening was employed to investigate SLC12A8-mediated oncogenic signaling pathway in lung cancer. SLC12A8 is a predictive biomarker of poor prognosis in lung cancer, particularly in patients with EGFR mutations. SLC12A8 overexpression diminishes the effectiveness of TKIs in EGFR-mutant lung cancer, resulting in treatment failure and disease progression. More importantly, SLC12A8-induced TKI resistance is mediated by the PDK1/AKT signaling axis, while silencing SLC12A8 expression inhibits oncogenic PDK1/AKT signaling, restoring TKI sensitivity in lung cancer cells. SLC12A8 mediates TKI resistance in EGFR-mutant lung cancer via PDK1/AKT axis. These findings not only advance our understanding of the molecular mechanisms driving TKI resistance, but also offer novel alternative strategies for the treatment of lung cancer.

NOX4 Upregulation in Lung Cancer: A Potential Therapeutic Target Associated with Immune Infiltration

Lung cancer is a common and highly lethal tumor worldwide. Research indicates that NOX4 plays a crucial role in apoptosis resistance and sustained proliferation of cancer cells in various types of tumors. In this study, NOX4 expression in lung cancer tissues was analyzed using the Wilcoxon rank sum test, while the Kruskal-Wallis Test was employed to explore the relationship between NOX4 expression and clinical characteristics in lung cancer patients. Prognostic evaluation was conducted using Kaplan-Meier plotter analysis, Cox regression, and receiver operating characteristic (ROC) curve construction. Gene set enrichment analysis (GSEA) was performed to investigate the correlation between NOX4 and immune infiltration. Results showed significantly higher NOX4 expression in lung cancer patients compared to normal tissues. High NOX4 expression was associated with shorter overall survival (OS) in lung cancer patients, as confirmed by Cox analysis. Furthermore, other clinicopathological factors predicted poor prognosis in lung adenocarcinoma (LUAD), and NOX4 demonstrated diagnostic value according to ROC analysis. Additionally, NOX4 overexpression correlated with macrophages and Th1 cells based on SsGSEA analysis. In summary, NOX4 serves as an independent prognostic biomarker and is associated with immune infiltration in lung cancer.

MiR-144-3p inhibits the proliferation and metastasis of lung cancer A549 cells via targeting HGF

AimMicroRNAs have been confirmed as vital regulators in gene expression, which could affect multiple cancer cell biological behaviors. This study aims to elucidate the molecular mechanism of miR-144-3p in lung cancer cellular proliferation and metastasis.MethodsMiR-144-3p expression in lung cancer tissues and cell lines was detected by qRT-PCR. HGF was predicted as the target gene of miR-144-3p using TargetScan and dual luciferase reporter assay. Immunohistochemistry and qRT-PCR were used to explore the impacts of HCF on lung cancer tissues and cell lines. Impacts of miR-144-3p and HGF on cancer cellular proliferation, migration and invasion were elucidated by CCK-8, Flow cytometry, Transwell invasion and Wound-healing assay. Moreover, nude mouse xenograft model was established to evaluate the effects of miR-144-3p on lung cancer cells.ResultsMiR-144-3p exhibited a reduction in both lung cancer tissues and cell lines. HGF was a direct target of miR-144-3p. In contrast to the miR-144-3p expression level, HGF showed a higher level in lung cancer tissues and cell lines. Overexpression miR-144-3p suppressed A549 and NCI-H1299 cell proliferation and metastasis, whereas this was reversed by HGF. MiR-144-3p exhibited an inhibitory effect on A549 cell-induced tumor growth of nude mice.ConclusionsThis study reveals miR-144-3p/HGF axis may be involved in the suppression of lung cancer cellular proliferation and development, and miR-144-3p may function as a potential therapeutic target in lung cancer treatment in the future.

FAM83A antisense RNA 1 (FAM83A-AS1) silencing impairs cell proliferation and induces autophagy via MET-AMPKɑ signaling in lung adenocarcinoma

ABSTRACT Studies demonstrate that long non-coding RNAs (lncRNAs) play vital roles in cancer progression. However, the expression pattern and molecular mechanisms of lncRNA FAM83A-AS1 in lung cancer remain largely unclear. Here, we analyzed FAM83A-AS1 expression in lung cancer tissues from three RNA-sequencing (RNA-Seq) datasets and validated these results using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in an independent set of lung adenocarcinoma. Cell proliferation, migration, invasion, and autophagy were analyzed after knockdown FAM83A-AS1 with siRNAs. The underlying molecular mechanisms of FAM83A-AS1 were performed by Western blot, qRT-PCR, and RNA-seq analysis. We found that FAM83A-AS1 was up-regulated in lung cancer and elevated expression was associated with poor patient survival. These results were confirmed using RT-PCR in an independent set of lung cancer. Functional study indicated that FAM83A-AS1 knockdown reduced cell proliferation, migration, invasion, and colony formation in cancer cells. FAM83A-AS1 silencing induced autophagy and cell cycle arrest at G2. Mechanistically, serval oncogenic proteins such as EGFR, MET, PI3K, and K-RAS were decreased upon FAM83A-AS1 silencing, while phosphor AMPKα and ULK1 were increased. Based on the above results, we believe that FAM83A-AS1 may have potential as a diagnosis/prognosis marker and its oncogenic role and autophagy regulation may be through MET-AMPKα signaling, which could lead to potential targeting for lung cancer therapy.

PLAC8 Overexpression Promotes Lung Cancer Cell Growth via Wnt/β-Catenin Signaling.

The PLAC8 expression in lung cancer tissues and in vitro grown lung cancer cells, as well as the involvement of the Wnt/β-Catenin signaling pathway, was investigated in this process. PLAC8 protein expression in human lung cancer tissues and lung tumor cells of different strains was discovered using immunohistochemistry staining and Western blot, respectively. Animal models of PLAC8 overexpression and knockdown were created using lentivirus. The development in tumor tissue was seen both in vitro and vivo. The Wnt/β-Catenin signaling pathway played an important part in this process, as shown by the dual luciferase reporter gene system. PLAC8 expression was elevated in lung cancer tissues and plasma and decreased in plasma after lung tumor resection. PLAC8 upregulation promotes cell proliferation in vivo and in vitro, while PLAC8 downregulation inhibits cell viability and proliferation. The results of the dual luciferase reporter gene system suggest that PLAC8 can significantly activate the Wnt/β-Catenin signaling pathway in cells and can conduct signaling through it. A potential treatment targeting the prognosis of lung cancer patients may be PLAC8 overexpression, which promotes the lung cancer cell proliferation through controlling the Wnt/β-Catenin signaling pathway.

Mechanism of RNA circHIPK3 Involved in Resistance of Lung Cancer Cells to Gefitinib.

To study the mechanism of circular ribonucleic acid (RNA) circHIPK3 involved in the resistance of lung cancer cells to gefitinib, 110 patients with lung cancer were recruited as the research objects, and the tumor tissue and para-cancerous tissue of each patient's surgical specimens were collected and paraffinized to detect the expression of circHIPK3 in different tissues. Gefitinib drug-resistant cell line of lung cancer was constructed with gefitinib to detect cell apoptosis under different conditions. As a result, the relative expression of circHIPK3 in patients with tumor diameter no less than 3 cm was dramatically inferior to that in patients with tumor diameter less than 3 cm (P < 0.05). The relative expression of circHIPK3 in patients with TNM stage II/III was dramatically inferior to that in patients with tumor, node, and metastasis (TNM) stage I (P < 0.05). Expression of circHIPK3 in patients with lymph node metastasis was dramatically inferior to that in patients without lymph node metastasis (P < 0.05). Of the lung cancer tissues of patients with different TNM stages, only six patients had high expression, and the remaining 104 patients had low expression. Moreover, electrophoresis revealed that circHIPK3 can only be amplified in cDNA, but not in gDNA. Gefitinib-mediated apoptosis rate of lung cancer drug-resistant cell lines decreased notably. In summary, the circular RNA circHIPK3 may have a notably low expression in lung cancer tissues, whose low expression had a certain enhancement effect on the drug resistance of lung adenocarcinoma cells to gefitinib.

Heterogeneous nuclear ribonucleoprotein K promotes the progression of lung cancer by inhibiting the p53-dependent signaling pathway.

BackgroundHeterogeneous nuclear ribonucleoprotein K (hnRNPK) is a nucleic acid‐binding protein. Reportedly, hnRNPK is overexpressed in many human tumors, and such overexpression is associated with poor prognosis, implicating the role of hnRNPK as an oncogene during tumorigenesis. In this study, hnRNPK expression in lung cancer tissues was investigated.MethodsBriefly, hnRNPK was knocked down in lung cancer cell lines, and effects of knockdown on the cell proliferation, migration, and cell cycle were assessed using a cell counting kit‐8 (CCK‐8) assay, colony formation assay, transwell assay and flow cytometry. The effects of hnRNPK knockdown on the p53‐dependent signaling pathway were examined using western blotting. Finally, the effect of hnRNPK knockdown on tumor growth was verified in vivo using a lung cancer xenograft mouse model.ResultshnRNPK knockdown inhibited the cell proliferation, migration and cell cycle. In addition to phenotypic changes, hnRNPK knockdown upregulated expressions of pCHK1, pCHK2, and p53，p21，cyclin D1, thereby mediating the DNA damage response (DDR). The regulatory function of hnRNPK during p53/p21/cyclin D1 signaling in hnRNPK‐knockdown A549 cells was confirmed by suppressed the protein expression of associated signaling pathways, which inhibited DDR.ConclusionhnRNPK plays a crucial role in the progression of lung cancer, ultimately affecting survival rate. Inhibition of progression of lung cancer cells induced by hnRNPK‐knockdown is dependent on activation of p53 by the p53/p21/cyclin D1 pathway.

Role of lncRNA FAM83H antisense RNA1 (FAM83H-AS1) in the progression of non-small cell lung cancer by regulating the miR-545-3p/heparan sulfate 6-O-sulfotransferase (HS6ST2) axis

ABSTRACT Long non-coding RNAs (lncRNAs) are crucial regulators of cancer pathogenesis and are potentially useful diagnostic and prognostic biomarker tools. FAM83H antisense RNA1 (FAM83H-AS1) has been reported to be a vital regulator of different cancers; however, little attention has been paid to its significance in lung cancer. Non-tumorigenic lung cell line BEAS-2B and adenocarcinoma lung cancer cell lines NCI-H1299 and HCC827 were used in the present study. In addition, RNA immunoprecipitation, Western blotting, quantitative reverse transcription-PCR (qRT-PCR), and luciferase reporter assays were used to dissect the role of FAM83H-AS1 in lung cancer progression. The results revealed that FAM83H-AS1 is highly expressed in lung cancer tissues, and its knockdown inhibits lung cancer cell invasion and proliferation reducing tumor growth in vivo. Besides, we found that FAM83H-AS1 targets miR-545-3p, and a negative correlation exists between their expression in lung cancer tissues. Simultaneously, miR-545-3p negatively regulates heparan sulfate 6-O-sulfotransferase (HS6ST2). Moreover, inhibition of miR-545-3p promoted HS6ST2 protein expression and lung cancer cell invasion. FAM83H-AS1 favors non-small cell lung cancer by targeting the miR-545-3p/HS6ST2 axis, supporting the possibility of developing FAM83H-AS1 as a target for NSCLC intervention.

P2RY14 downregulation in lung adenocarcinoma: a potential therapeutic target associated with immune infiltration.

BackgroundThe current study aimed to investigate the interrelation between P2RY14 and the prognosis of patients suffering from lung adenocarcinoma (LUAD) following surgery.MethodsThe differentially expressed gene (DEG) P2RY14 was screened by the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Immunology Database and Analysis Portal (ImmPort) databases. The relationship between P2RY14 and clinical data of LUAD was analyzed in TCGA and Kaplan-Meier (KM)-plotter databases. The association of P2RY14 with immune cells and immune-related expressed genes was analyzed in the Tumor Immune Estimation Resource (TIMER) database. A retrospective analysis of the 100 patients clinical data undergoing pulmonary adenocarcinoma surgery admitted to Nanjing Chest Hospital. Immunohistochemistry (IHC) analysis was carried out to evaluate the P2RY14 expression in lung cancer tissues, and quantitative reverse transcription PCR (RT-qPCR) was used to confirm the mRNA expression of this gene in LUAD tissues. And their survival was evaluated. KM method and the log-rank test were used for univariate survival analysis, and the Cox regression method was employed for multivariate survival analysis.ResultsP2Y14 was the DEG identified by the database. P2Y14 expression was upregulated in para-cancer tissues in comparison to cancer tissues. Patients suffering from LUAD who have high P2RY14 expression had a better prognosis than those with low expression. P2RY14 expression was shown to be substantially linked with immune invasion in the TIMER database. Finally, the trial included 100 patients, of which 80 died and 20 survived with a mean overall survival (OS) of 48 months. Between the high and low expression groups of P2RY14, there were statistically significant variations in the clinical stage and differentiation degree (P<0.05). Cox regression analysis revealed that differentiation degree, smoking history, and P2RY14 expression were independent risk factors for the prognosis of LUAD patients (all P<0.05).ConclusionsP2RY14 can substantially prolong the OS of patients suffering from LUAD and can be utilized as a new LUAD predictive biomarker. P2RY14 may be related to LUAD immune invasion and have an essential role in inhibiting tumor cell immune escape within the LUAD microenvironment.

HNMT Upregulation Induces Cancer Stem Cell Formation and Confers Protection against Oxidative Stress through Interaction with HER2 in Non-Small-Cell Lung Cancer.

Background: The treatment of non-small-cell lung cancer (NSCLC) involves platinum-based chemotherapy. It is typically accompanied by chemoresistance resulting from antioxidant properties conferred by cancer stem cells (CSCs). Human epidermal growth factor receptor 2 (HER2) enhances CSCs and antioxidant properties in cancers, including NSCLC. Methods: Here, we elucidated the role of histamine N-methyltransferase (HNMT), a histamine metabolism enzyme significantly upregulated in NSCLC and coexpressed with HER2. HNMT expression in lung cancer tissues was determined using quantitative reverse transcription PCR (RT-qPCR). A publicly available dataset was used to determine HNMT’s potential as an NSCLC target molecule. Immunohistochemistry and coimmunoprecipitation were used to determine HNMT–HER2 correlations and interactions, respectively. HNMT shRNA and overexpression plasmids were used to explore HNMT functions in vitro and in vivo. We also examined miRNAs that may target HNMT and investigated HNMT/HER2’s role on NSCLC cells’ antioxidant properties. Finally, how HNMT loss affects NSCLC cells’ sensitivity to cisplatin was investigated. Results: HNMT was significantly upregulated in human NSCLC tissues, conferred a worse prognosis, and was coexpressed with HER2. HNMT depletion and overexpression respectively decreased and increased cell proliferation, colony formation, tumorsphere formation, and CSCs marker expression. Coimmunoprecipitation analysis indicated that HNMT directly interacts with HER2. TARGETSCAN analysis revealed that HNMT is a miR-223 and miR-3065-5p target. TBHp treatment increased HER2 expression, whereas shHNMT disrupted the Nuclear factor erythroid 2-related factor 2 (Nrf2)/ hemeoxygenase-1 (HO-1)/HER2 axis and increased reactive oxygen species accumulation in NSCLC cells. Finally, shHNMT sensitized H441 cells to cisplatin treatment in vitro and in vivo. Conclusions: Therefore, HNMT upregulation in NSCLC cells may upregulate HER2 expression, increasing tumorigenicity and chemoresistance through CSCs maintenance and antioxidant properties. This newly discovered regulatory axis may aid in retarding NSCLC progression and chemoresistance.

XIST/miR-34a-5p/PDL1 axis regulated the development of lung cancer cells and the immune function of CD8+ T cells

Purpose Long non-coding RNA (lncRNA) XIST has been shown to be involved in the immune escape of breast cancer, but it is unclear whether it is involved in the immune escape of lung cancer, so it will be discussed in this study. Methods XIST and miR-34a-5p expression in lung cancer tissues and cells were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The targeting relationship between miR-34a-5p and XIST/programmed cell death receptor ligand 1 (PDL1) was predicted by bioinformatics website and verified by dual-luciferase report experiment. After co-transfection with XIST specific short hairpin RNA (sh-XIST) and miR-34a-5p inhibitors, the changes in PDL1 expression, and cell biological behavior were detected by qRT-PCR, cell counting kit 8, flow cytometry, and Transwell experiments. Similarly, after co-transfection of PDL1 specific small interfering RNA (siPDL1) and miR-34a-5p inhibitors, the changes in cell biological behavior were detected again. After CD8+ T cells were co-cultured with lung cancer cells transfected with sh-XIST and miR-34a-5p inhibitors, the expression of cytokines and immunosuppressive molecules was detected by western blot and enzyme-linked immunosorbent assay (ELISA). Results XIST was up-regulated in lung cancer tissues, while miR-34a-5p was the opposite. XIST up-regulated the expression of PDL1 by targeting miR-34a-5p, thereby affecting the viability, apoptosis, migration, and invasion of lung cancer cells. In the co-culture system, XIST targeted miR-34a-5p to inhibit cytokines secretion and promote the expression of immunosuppressive molecules. Conclusions XIST/miR-34a-5p/PDL1 axis was involved in the malignant biological behavior of lung cancer cells and the immune function of CD8+ T cells.

UTMD-mediated delivery of miR-21-5p inhibitor suppresses the development of lung cancer

Background: Ultrasound-targeted microbubble destruction (UTMD) is a new type of gene delivery technology. MiR-21-5p was highly expressed in a variety of cancers. In this paper, miR-21-5p inhibitor was transfected into lung cancer cells by UTMD to observe its role in lung cancer.Methods: StarBase was used to analyze the miR-21-5p expression in lung cancer patients and its relationship with the prognosis of the patients. MiR-21-5p expression in lung cancer tissues or cell lines was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Effects of gradient concentration (0, 5, 10, 20, 30%) of SonoVue or gradient mechanical index (MI) (0, 0.5, 1, 1.5, 2 W/cm2) on the cell viability were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The targeting relationship between miR-21-5p and B-cell translocation gene 2 (BTG2) was predicted by TargetScan and confirmed by dual-luciferase reporter assay, while the expressions of the two genes were determined by qRT-PCR. Through liposome transfection or UTMD transfection, the effects of miR-21-5p/BTG2 on the biological behaviors of lung cancer cells, the size of xenograft tumors and the expressions of ki67 and miR-21-5p were measured by qRT-PCR, western blot, cell function experiments and immunohistochemistry, respectively.Results: MiR-21-5p expression was upregulated in lung cancer, which was associated with a poor prognosis. The optimal ultrasound conditions were 10% SonoVue concentration and 1 W/cm2. UTMD transfection exerted a stronger effect than liposome transfection. MiR-21-5p promoted cell viability, proliferation and migration yet suppressed apoptosis by targeting BTG2. MiR-21-5p inhibitor reduced the size and volume of xenograft tumor and the expressions of ki67 and miR-21-5p in xenograft tumor tissues. ConclusionUTMD-mediated miR-21-5p inhibitor can more effectively suppress the development of lung cancer.

DYNC1H1 regulates NSCLC cell growth and metastasis by IFN-γ-JAK-STAT signaling and is associated with an aberrant immune response

It is urgent to identify new biomarkers and therapeutic targets to ameliorate the clinical prognosis of patients with lung cancer. The functional significance and molecular mechanism of dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) in nonsmall cell lung cancer (NSCLC) progression is still elusive. In our current study, publicly available data and Western blotting experiments confirmed that DYNC1H1 expression was upregulated in lung cancer samples compared with noncancerous samples. Quantitative real-time PCR (qPCR) results indicated that high DYNC1H1 expression in lung cancer tissues was significantly associated with clinical tumor stage and distal metastasis; moreover, its high expression was negatively correlated with prognosis. Functional experiments demonstrated that DYNC1H1 loss of function caused a significant decrease in cell viability and cell proliferative ability, inhibition of the cell cycle, and promotion of both migration potential and invasion potential in vitro. Animal experiments by tail vein injection of lung cancer cells showed that DYNC1H1 knockdown significantly decreased lung cancer metastasis. Mechanistically, the results from a human protein array showed changes in the IFN-γ-JAK-STAT signaling pathway, and analysis of The Cancer Genome Atlas (TCGA) immune data demonstrated that disturbance of the immune microenvironment might be involved in the impaired growth and metastatic ability mediated by DYNC1H1 loss in NSCLC. DYNC1H1 might serve as a promising biological marker of prognosis and a potential clinical therapeutic target for patients with NSCLC.