Exosomal transfer of miR-195-5p restrains lung adenocarcinoma progression.

Exosome is an important way for tumor cells to communicate with other cells and plays an important role in tumor progression. Previous studies revealed that miR-195-5p acts as a tumor suppressor in lung cancer. However, the role and molecular mechanism of exosomal transferred miR-195-5p in lung adenocarcinoma (LAC) remains unknown. Here, we found that miR-195-5p expression in circulating exosomes of LAC patients was lower than that of healthy controls. Meanwhile, the expression of exosomal miR-195-5p from normal bronchial epithelial cell line BEAS-2B cells was significantly higher than that of lung cancer cell lines. The exosome labeling assay confirmed that BEAS-2B cells-derived exosomes could be captured by lung cancer cells. Furthermore, exosomal miR-195-5p derived from BEAS-2B cells remarkably inhibited the proliferation, migration, invasion of lung cancer cells, and tumor growth in vivo. In addition, exosomal miR-195-5p from BEAS-2B cells also suppressed the tube-forming ability of vascular endothelial cells. Moreover, we verified that miR-195-5p decreased apelin (APLN) expression to inactivate the Wnt signaling pathway, thereby inhibiting tumor invasiveness and angiogenesis. In conclusion, our research shows that exosomal miR-195-5p from normal bronchial epithelial cells hinders the progression of LAC, suggesting that regulation of exosomal miR-195-5p provides a novel strategy for LAC treatment.

LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved. METHODS: Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism. RESULT: Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting ß-TrCP1 mediated ubiquitin degradation of ß-catenin proteins, which in turn causes enhanced tumorigenesis. CONCLUSIONS: Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.

The characteristics of ctDNA reveal the high complexity in matching the corresponding tumor tissues.

BACKGROUND: Next-generation sequencing (NGS) is an efficient and sensitive method to detect mutations from ctDNA. Many features and clinical conditions could significantly affect the concordance between ctDNA and corresponding tumor tissues. Our goal was to systematically investigate the critical factors contributing to different concordance between ctDNA and corresponding tumor tissues. METHODS: We recruited two groups of IIIB or IV lung cancer patients: The standard group to evaluate the accuracy of our method and the concordance between ctDNA and tumor tissues, and the study group with various clinical conditions. We applied our unique identification (UID) indexed capturing-based sequencing (UC-Seq) to ctDNA samples, and confirm the results by Droplet digital PCR (ddPCR). RESULTS: Considering mutations detected from NGS of tumor tissues as golden standard, UC-Seq achieved overall 93.6% sensitivity for SNVs and Indels, and 0.8 Pearson correlation between tumor TMB and bTMB. Efficacious treatments, long sampling date (more than 2 weeks) between tumor tissues and ctDNA and low concentrations of cfDNA (less than 9 ng/ml) could significantly decrease the concordance between ctDNA and tumor tissues. About 84% mutations showed shorter mutant fragment length than that of wild-type fragments, and the AFs of mutations could be significantly enriched in small-size ctDNA. CONCLUSIONS: In late-stage lung cancer patients, ctDNA generally has high concordance with tumor tissues. However it could be significantly affected by three clinical conditions which could dynamically change the content of ctDNA. Moreover, the detection limit could be further extended by enriching small-size ctDNA in the preparation of samples.

MicroRNA-30e-5p promotes cell growth by targeting PTPN13 and indicates poor survival and recurrence in lung adenocarcinoma.

Aberrant microRNA expression is involved in the regulation of various cellular processes, such as proliferation and metastasis in multiple diseases including cancers. MicroRNA-30e-5p (miR-30e) was previously reported as an oncogenic or tumour suppressing miRNA in some malignancies, but its function in lung adenocarcinoma (LAC) remains largely undefined. In this study, we found that the expression of miR-30e was increased in LAC tissues and cell lines, associated with tumour size and represented an independent prognostic factor for overall survival and recurrence of LAC patients. Further functional experiments showed that knockdown of miR-30e suppressed cell growth while its overexpression promoted growth of LAC cells and xenografts in vitro and in vivo. Mechanistically, PTPN13 was identified as the direct target of miR-30e in LAC, in which PTPN13 expression was down-regulated in LAC tissues and showed the inverse correlation with miR-30e expression. Overexpression of PTPN13 inhibited cell growth and rescued the proliferation-promoting effect of miR-30e through inhibition of the EGFR signalling. Altogether, our findings suggest that miR-30e could function as an oncogene in LAC via targeting PTPN13 and act as a potential therapeutic target for treating LAC.

Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

Corrigendum: Comprehensive pan-cancer analysis of the prognostic and immunological roles of the METTL3/lncRNA-SNHG1/miRNA-140-3p/UBE2C axis.

[This corrects the article DOI: 10.3389/fcell.2021.765772.].

Immune-Related miRNA-195-5p Inhibits the Progression of Lung Adenocarcinoma by Targeting Polypyrimidine Tract-Binding Protein 1.

Purpose: Lung adenocarcinoma (LUAD) is the most common type of cancer and the leading cause of cancer-related death worldwide, resulting in a huge economic and social burden. MiRNA-195-5p plays crucial roles in the initiation and progression of cancer. However, the significance of the miRNA-195-5p/polypyrimidine tract-binding protein 1 (miRNA-195-5p/PTBP1) axis in the progression of lung adenocarcinoma (LUAD) remains unclear. Methods: Data were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The starBase database was employed to examine the expression of miRNA-195-5p, while the Kaplan-Meier plotter, UALCAN, and Gene Expression Profiling Interactive Analysis (GEPIA) databases were utilized to analyze the tumor stage and prognostic value of miRNA and PTBP1. Quantitative reverse transcription-polymerase chain reaction assay was conducted to detect the expression levels of miRNA-195-5p in LUAD cell lines and tissues. The effects of miRNA-195-5p on cell proliferation and migration were examined using the cell growth curve, clone information, transwell assays, and wound healing assays. Results: We found that miRNA-195-5p was down-regulated in LUAD cancer and cell lines. Importantly, its low levels were related to the tumor stage, lymph node metastasis, and poor prognosis in LUAD. Overexpression of miR-195-5p significantly inhibited cell growth and migration promotes cell apoptosis. Further study revealed that PTBP1 is a target gene of miRNA-195-5p, and overexpression of miRNA-195-5p inhibited the progression of LUAD by inhibiting PTBP1 expression. MiRNA-195-5p expression was related to immune infiltration in lung adenocarcinoma. Moreover, PTBP1 was negatively correlated with diverse immune cell infiltration and drug sensitivity. Conclusion: Our findings uncover a pivotal mechanism that miRNA-195-5p by modulate PTBP1 expression to inhibit the progression of LUAD. MiRNA-195-5p could be a novel diagnostic and prognostic molecular marker for LUAD.

Comprehensive Analyses of the Immunological and Prognostic Roles of an IQGAP3AR/let-7c-5p/IQGAP3 Axis in Different Types of Human Cancer.

IQ motif containing GTPase-activating protein 3 (IQGAP3) is a member of the Rho family of guanosine-5'-triphosphatases (GTPases). IQGAP3 plays a crucial part in the development and progression of several types of cancer. However, the prognostic, upstream-regulatory, and immunological roles of IQGAP3 in human cancer types are not known. We found that IQGAP3 expression was increased in different types of human cancer. The high expression of IQGAP3 was correlated with tumor stage, lymph node metastasis, and a poor prognosis in diverse types of human cancer. The DNA methylation of IQGAP3 was highly and negatively correlated with IQGAP3 expression in diverse cancer types. High DNA methylation in IQGAP3 was correlated with better overall survival in human cancer types. High mRNA expression of IQGAP3 was associated with tumor mutational burden, microsatellite instability, immune cell infiltration, and immune modulators. Analyses of signaling pathway enrichment showed that IQGAP3 was involved in the cell cycle. IQGAP3 expression was associated with sensitivity to a wide array of drugs in cancer cells lines. We revealed that polypyrimidine tract-binding protein 1 (PTBP1) and an IQGAP3-associated lncRNA (IQGAP3AR)/let-7c-5p axis were potential regulations for IQGAP3 expression. We provided the first evidence to show that an IQGAP3AR/let-7c-5p/IQGAP3 axis has indispensable roles in the progression and immune response in different types of human cancer.

Deciphering the Role of Shugoshin-Like Protein 1 in Lung Adenocarcinoma: A Comprehensive Analysis and In Vitro Study.

Shugoshin-like protein 1 (SGO1) has been characterized in its function in correct cell division and its role in centrosome cohesion in the nucleus. However, the underlying biological function and potential mechanisms of SGO1 driving the progression of lung adenocarcinoma remain unclear. In this study, we found that SGO1 was increased in LUAD tissues and cell lines. Upregulation of SGO1 expression was correlated with poor overall survival (OS), disease-free survival (DSS), and progression-free survival (PFS) in patients with LUAD. ROC curve analysis suggested that the AUC value of SGO1 was 0.983. Correlation analysis showed that SGO1 expression was related to immune infiltration in LUAD. Meanwhile, a potential ceRNA network was constructed to identify the lncRNA-MIR4435-2HG/miR-125a-5p/SGO1 regulatory axis in LUAD. Finally, we determine that SGO1 regulated the cell proliferation and cell apoptosis of lung adenocarcinoma in vitro. In conclusion, our data suggested that SGO1 could be a novel prognostic biomarker for lung adenocarcinoma.

Long Non-Coding RNA-TMPO-AS1 as ceRNA Binding to let-7c-5p Upregulates STRIP2 Expression and Predicts Poor Prognosis in Lung Adenocarcinoma.

Background: Striatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth. But the role of STRIP2 in lung adenocarcinoma (LUAD) has not been discovered clearly. Thus, the aim of our study is to explore the function and underlying mechanism of STRIP2 in LUAD. Methods: Expression of STRIP2 was determined using the Cancer Genome Atlas (TCGA), GTEx, Ualcan, and the Human Protein Altas databases. The Correlation of STRIP2 and survival was detected by PrognoScan and Kaplan-Meier plotter databases. Besides, the correlation between STRIP2 expression and tumor immune infiltration as well as immune checkpoints were analyzed by the ssGSEA method. The biological function of STRIP2 and its co-expression genes was determined by gene ontology (GO) and Genes and Genomes (KEGG), respectively. Finally, the expression level and biological function of STRIP2 in LUAD were determined by qPCR, CCK8, transwell, and wound healing assays. Results: This manuscript revealed a significantly increased expression of mRNA and protein of STRIP2 in lung adenocarcinoma compared with the adjacent normal tissues. GEO and Kaplan-Meier plotter databases showed higher STRIP2 expression levels were correlated with poor prognosis survival of LUAD. Moreover, Cox regression analysis suggested that a higher STRIP2 level served as an independent risk factor in predicting deteriorative overall survival (OS) for LUAD patients. SsGSEA results showed STRIP2 expression level was positively correlated with infiltrating levels of Th2 cells in LUAD. Lastly, GO analysis indicated the biological processes were enriched in nuclear division and positive regulation of the cell cycle. KEGG signaling pathway analysis showed STRIP2 was correlated with the MAPK signaling pathway and the TNF signaling pathway. The GSEA database showed that STRIP2 was positively associated with the epithelial-mesenchymal transition, cell cycle, and TNF signaling pathway. The QRT-PCR assay showed that STRIP2 was upregulated in LUAD cell lines. Cell proliferation and migration were inhibited in LUAD by knockdown of STRIP2. Moreover, we confirmed that the TMPO-AS1/let-7c-5p/STRIP2 network regulates STRIP2 overexpression in LUAD and is associated with poor prognosis. Conclusion: Our findings indicated that STRIP2 acted as a crucial oncogene in LUAD and was correlated with unfavorable survival and tumor infiltration inflation.

Identification and Validation Prognostic Impact of MiRNA-30a-5p in Lung Adenocarcinoma.

MiRNA-30a-5p is a microRNA found to be decreased in various human cancers, including lung adenocarcinoma (LUAD). However, the molecular mechanisms of miRNA-30a-5p involve in the progression of LUAD remains unclear. In this study, we found that miRNA-30a-5p expression was significantly decreased in LUAD cells lines, LUAD tissues, and peripheral blood serum. Besides, LUAD patients with decreased miRNA-30a-5p expression exhibit worse clinical outcomes compared to the patients with higher miRNA-30a-5p expression, decreased expression of miRNA-30a-5p was associated with advanced clinical outcomes. Receiver operating characteristic (ROC) curve analysis of miRNA-30a-5p showed an area under the curve (AUC) value of 0.902, indicating its prognostic value in LUAD. Moreover, immune infiltration and gene set enrichment analysis (GSEA) enrichment analyze demonstrated that miRNA-30a-5p expression was associated with immune cell infiltrated in LUAD. Finally, we found that miRNA-30a-5p inhibits cell proliferation, migration, and self-renewal abilities of LUAD in vitro. In summary, this is the first report that miRNA-30a-5p correlated with progression and immune infiltration, which shed some lights on potential prognostic and therapeutic biomarker for LUAD.

Corrigendum: Identification and Validation Prognostic Impact of miRNA-30a-5p in Lung Adenocarcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.831997.].

Corrigendum: Comprehensive pan-cancer analysis of the prognostic and immunological roles of METTL3/lncRNA-SNHG1/miRNA-140-3p/UBE2C axis.

[This corrects the article DOI: 10.3389/fcell.2021.765772.].

Corrigendum: Long non-coding RNA-TMPO-AS1 as ceRNA binding to let-7c-5p upregulates STRIP2 expression and predicts poor prognosis in lung adenocarcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.921200.].

NcRNA-Mediated High Expression of HMMR as a Prognostic Biomarker Correlated With Cell Proliferation and Cell Migration in Lung Adenocarcinoma.

Background: Hyaluronan-mediated motility receptor (HMMR) plays a pivotal role in cell proliferation in various cancers, including lung cancer. However, its function and biological mechanism in lung adenocarcinoma (LUAD) remain unclear. Methods: Data on HMMR expression from several public databases were extensively analyzed, including the prognosis of HMMR in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using DAVID and gene set enrichment analysis (GSEA) software. The correlation between HMMR expression and immune cell infiltration was analyzed in the Tumor Immune Estimation Resource (TIMER) database, and the gene and protein networks were examined using the GeneMANIA and STRING databases. Experimentally, the expression of HMMR in LUAD and lung cancer cell lines was determined using immunohistochemistry and quantitative RT-PCR assays. Besides, the function of HMMR on cancer cell proliferation and migration was examined using cell growth curve and colony formation, Transwell, and wound healing assays. Results: In this study, we found that HMMR was elevated in LUAD and that its high expression was associated with poor clinicopathological features and adverse outcomes in LUAD patients. Furthermore, our results demonstrated that the expression of HMMR was positively correlated with immune cell infiltration and immune modulation. Interestingly, diverse immune cell infiltration affects the prognosis of LUAD. In the functional assay, depletion of HMMR significantly repressed the cancer cell growth and migration of LUAD. Mechanically, we found that that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of HMMR in LUAD. Depletion of TMPO-AS1 and overexpression of let-7b-5p could result in the decreased expression of HMMR in LUAD cells. Furthermore, we found that TMPO-AS1 was positively correlated with HMMR, yet negatively correlated with let-7b-5p expression in LUAD. Conclusions: Our findings elucidated that the DNA methylation/TMPO-AS1/let-7b-5p axis mediated the high expression of HMMR, which may be considered as a biomarker to predict prognosis in LUAD.

Identification and Validation of Long Non-Coding RNA LCIIAR as a Biomarker in LUAD.

Lung cancer is the leading cause of cancer-related death worldwide. Therapies for lung cancer have relatively poor outcomes and need to be improved. Lung cancer immune cell infiltration associated RNA (LCIIAR) is a long noncoding RNA (lncRNA), which is overexpressed in human cancers. However, the clinical significance and functional role of LCIIAR in Lung Adenocarcinoma remain unclear. Here, we identified a novel long non-coding RNA (ENSG00000256802), termed LCIIAR (lung cancer immune cell infiltration associated lncRNA), up-regulated in lung cancer tissue and cell lines. We show that increase LCIIAR expression correlated with poor clinical stage and adverse clinical outcomes and that could also serve as an independent unfavorable prognostic factor in patients with Lung Adenocarcinima. GSEA analysis demonstrated that LCIIAR is mainly involved in the regulation of the immune response. We uncovered that elevate LCIIAR expression positively correlated with immune infiltration and immune modulator in Lung Adenocarcinoma. More importantly, we confirmed that silencing of LCIIAR expression significantly inhibits the proliferation, and migration abilities of these tumour cells. We also demonstrated that the LCIIAR/hsa-miR184/SLC16A3/CDCP1 network regulates SLC16A3/CDCP1 overexpression in and is associated with poor prognosis in this tumour. Therefore our findings revealed the critical role of LCIIAR in Lung Adenocarcinoma progression, which may also serve as a prognostic biomarker and novel therapeutic target.

Comprehensive Analysis of the Prognostic and Immunological Role of PAFAH1B in Pan-Cancer.

Platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3) plays a critical role in cancer initiation, metastasis, and progression; however, it remains unknown how PAFAH1B3 impacts cancer diagnosis and prognosis or regulates the immune response to different types of cancer. In this study, PAFAH1B3 was elevated in human pan-cancer, and this correlated with greater pathology and poor prognosis, in particular for non-small cell lung cancer (NSCLC) and liver hepatocellular carcinoma (LIHC). In addition, PAFAH1B3 expression was positively associated with tumor mutational burden (TMB), microsatellite instability (MSI), immune cell infiltration, immune-modulatory related gene expression, and diverse cancer drug sensitivity in human cancer. Increased PAFAH1B3 expression correlated with poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) of NSCLC and LIHC, and has potential as an independent risk factor for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) during LIHC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis confirmed that PAFAH1B3 is primarily involved in immune regulation. More importantly, results demonstrated that PAFAH1B3 was upregulated in liver cancer cells lines and that knockdown of this gene significantly inhibited cell proliferation, migration, and invasion in liver hepatocellular carcinoma (LIHC). In summary, this study elucidates the clinical significance and biological function of PAFAH1B3 during liver hepatocellular carcinoma (LIHC) and may serve as a potential biomarker for the diagnosis and prognosis of various cancer types.

Comprehensive Pan-Cancer Analysis of the Prognostic and Immunological Roles of the METTL3/lncRNA-SNHG1/miRNA-140-3p/UBE2C Axis.

Growing evidence has demonstrated that UBE2C plays a critical role in cancer progression, but there is no study focusing on the prognosis, upstream regulation mechanism, and immunological roles of UBE2C across diverse tumor types. In this study, we found that UBE2C was elevated in this human pan-cancer analysis, and high expression of UBE2C was correlated with poor prognosis. In addition, UBE2C expression was markedly associated with tumor mutation burden (TMB), microsatellite instability (MSI), immune cell infiltration, and diverse drug sensitivities. Finally, we showed that the METTL3/SNHG1/miRNA-140-3p axis could potentially regulate UBE2C expression. N(6)-Methyladenosine (m6A) modifications improved the stability of methylated SNHG1 transcripts by decreasing the rate of RNA degradation, which lead to upregulation of SNHG1 in non-small cell lung cancer (NSCLC). In vitro functional experiments showed that SNHG1, as a competing endogenous RNA, sponges miR-140-3p to increase UBE2C expression in NSCLC cell lines. Our study elucidates the clinical importance and regulatory mechanism of the METTL3/SNHG1/miRNA-140-3p/UBE2C axis in NSCLC and provides a prognostic indicator, as well as a promising therapeutic target for patients with NSCLC.

SNX20AR/MiRNA-301a-3p/SNX20 Axis Associated With Cell Proliferation and Immune Infiltration in Lung Adenocarcinoma.

Lung cancer is the most common tumor with severe morbidity and high mortality. Increasing evidence has demonstrated that SNX20 plays crucial roles in the progression of human cancer. However, the functions and mechanism of SNX20 in LUAD are still barely known. Here, we employ the TCGA, GEO and CCLE databases to examine the expression of SNX20 in human varies cancer, the results shown that SNX20 is down-regulated in lung Adenocarcinoma, SNX20 level was significantly positive correlated with poor prognosis and lung cancer immune cell infiltration. We found that over-expression of SNX20 significantly restrain NSCLC cell proliferation and migration. Subsequently, we discover a network regulating SNX20 in LUAD, further study found that the decreased of the SNX20 likely caused by DNA hypermethylation. Furthermore, we identified that SNX20AR/miRNA-301a-3p mediated decreased of SNX20 correlated with lung cancer progression and cancer immune infiltration in LUAD. Our findings suggested that ncRNAs play a crucial role in the regulatory network of SNX20. Collectively, our findings demonstrate the suppressor roles of the SNX20AR/miRNA-301a-3p/SNX20 axis in Lung Adenocarcinoma, represent that SNX20 have the potential of as an effective therapeutic target in future.

Systematic Analysis and Validation of the Prognosis, Immunological Role and Biology Function of the Ferroptosis-Related lncRNA GSEC/miRNA-101-3p/CISD1 Axis in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer, accounting for approximately 85% of pulmonary malignancies. Emerging evidence has demonstrated that ferroptosis plays a central role in both immunities as well as tumor proliferation. However, the clinical significance, immunological function, and upstream modulatory mechanism of ferroptosis-related genes in LUAD remain unclear. Here, we utilized various bioinformatics data to identify differentially expressed (DEGs) and prognosis-related ferroptosis (FRGs) genes in LUAD. Based upon identified DEGs, FRG, and ceRNA modulatory networks were constructed. Pearson's correlation analysis was used to evaluate the correlation between FRGs and the tumor mutational burden, microsatellite instability, tumor-infiltrating immunity, cellular checkpoint control, and drug sensitivity in LUAD. A loss-of-function analysis was performed to verify the function of CISD1 in LUAD progression. Our findings revealed that certain FRGs (CISD1, ATP5MC3, PGD, SLC7A11, ACSL3, and FANCD2) are significantly upregulated in LUAD and that their elevated expression is associated with both advanced tumor stage and unfavorable prognosis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results revealed these FRGs to be primarily involved in ferroptosis and glutathione metabolism in LUAD. We constructed a prognostic FRG-based model capable of accurately predicting LUAD patient overall survival with high specificity. The upstream lncRNA GSEC/miRNA-101-3p regulatory axis involving CISD1, ATP5MC3, and PGD was identified to be relevant in tumor progression. We also found GSEC, CISD1, ATP5MC3, and PGD to be upregulated, with miRNA-101-3p downregulated, in the setting of LUAD. Immunohistochemical analysis revealed CISD1, ATP5MC3, and PGD overexpression in LUAD tissue samples; CISD1 knockdown was noted to significantly inhibit LUAD proliferation and migration. In summary, this study characterizes relevant functional roles of the lncRNA GSEC/miR-101-3p axis in the setting of LUAD and suggests diagnostic and therapeutic biomarkers potentially useful in the clinical management of this illness.