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.].

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.

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.

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.

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.

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.

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

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

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 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.

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.

MicroRNA-125b-5p Correlates With Prognosis and Lung Adenocarcinoma Progression.

A growing number of studies have focused on investigating microRNAs as crucial regulators in the progression of multiple cancer types. Nevertheless, the biological effects and immunological role of miR-125b-5p in non-small cell lung cancer (lung adenocarcinoma, LUAD) have not been determined. The present study aimed to examine the function of miR-125b-5p on cell proliferation and the outcomes of LUAD patients. We utilized diverse public databases in the analysis of the expression, prognosis, diagnostic value, and immune role of miR-125b-5p in non-small cell lung cancer. The growth curve, colony formation, flow cytometry, and Transwell and invasion assays were utilized to determine the function of miR-125b-5p in LUAD progression. In this study, we found that miR-125b-5p was decreased in LUAD and correlated with poor prognosis. Pathway analyses revealed that miR-125b-5p was mainly involved in cell proliferation and immune regulation. Moreover, in vitro experiments indicated that the overexpression of miR-125b-5p significantly inhibited cell proliferation, migration, and invasion and induced cell apoptosis of LUAD. Finally, we discovered that miR-125b-5p correlated with immune cell infiltration. In summary, these results demonstrated that miR-125b-5p serves as a prognostic marker and a therapeutic target for LUAD.

FOXM1/lncRNA TYMSOS/miR-214-3p-Mediated High Expression of NCAPG Correlates With Poor Prognosis and Cell Proliferation in Non-Small Cell Lung Carcinoma.

Lung cancer is the most common cancer with high mortality. Increasing evidence has demonstrated that nonstructural maintenance of chromosomes condensin I complex subunit G (NCAPG) plays a crucial role in the progression of human cancers. However, the biological function and underlying mechanism of NCAPG in non-small cell lung cancer (NSCLC) are still unclear. Here, we utilized diverse public databases to analyze the expression of NCAPG in pan-cancer. We found that NCAPG was highly expressed in various human cancers, especially in NSCLC. NCAPG expression was significantly positively correlated with poor clinical-pathological features, poor prognosis, tumor mutational burden, DNA microsatellite instability, and immune cell infiltration in NSCLC. In addition, our results showed that depletion of NCAPG significantly inhibited NSCLC cell proliferation, migration, and self-renewal abilities, yet these could be reversed by adding microRNA (miRNA)-214-3p. Knockdown of long noncoding RNA (lncRNA) thymidylate synthetase opposite strand (TYMSOS) also inhibits the NSCLC cell proliferation, migration, and self-renewal abilities. In summary, our findings demonstrated that the crucial roles of the FOXM1/lncRNA-TYMSOS/miRNA-214-3p/NCAPG axis in NSCLC may shed light on how NCAPG may act as a therapeutic target for NSCLC.