scholarly journals Regulation of Oncogenic Targets by Tumor-Suppressive miR-150-3p in Lung Squamous Cell Carcinoma

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1883
Author(s):  
Keiko Mizuno ◽  
Kengo Tanigawa ◽  
Shunsuke Misono ◽  
Takayuki Suetsugu ◽  
Hiroki Sanada ◽  
...  

Several recent studies have shown that both strands of certain miRNAs derived from miRNA duplexes are involved in cancer pathogenesis. Our own recent studies revealed that both strands of the miR-150 duplex act as tumor-suppressive miRNAs in lung adenocarcinoma (LUAD) through the targeting of several oncogenes. The aim of the study here was to further investigate the tumor-suppressive roles of miR-150-3p (the passenger strand) in lung squamous cell carcinoma (LUSQ) and its control of cancer-promoting genes in LUSQ cells. The downregulation of miR-150-3p in LUSQ tissues was confirmed by data in The Cancer Genome Atlas (TCGA). The ectopic expression of miR-150-3p attenuated cancer cell aggressive features, e.g., cell cycle arrest, migration and invasive abilities. Our target search strategy successfully identified a total of 49 putative targets that were listed as subjects of miR-150-3p regulation in LUSQ cells. Interestingly, among these targets, 17 genes were categorized as related to the “cell cycle” based on Gene Ontology (GO) classification, namely CENPA, CIT, CCNE1, CCNE2, TIMELESS, BUB1, MCM4, HELLS, SKA3, CDCA2, FANCD2, NUF2, E2F2, SUV39H2, CASC5, ZWILCH and CKAP2). Moreover, we show that the expression of HELLS (helicase, lymphoid specific) is directly controlled by miR-150-3p, and its expression promotes the malignant phenotype of LUSQ cells.

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1082
Author(s):  
Piotr Białas ◽  
Aleksandra Śliwa ◽  
Anna Szczerba ◽  
Anna Jankowska

Human chorionic gonadotropin (hCG) is a well-known hormone produced by the trophoblast during pregnancy as well as by both trophoblastic and non-trophoblastic tumors. hCG is built from two subunits: α (hCGα) and β (hCGβ). The hormone-specific β subunit is encoded by six allelic genes: CGB3, CGB5, CGB6, CGB7, CGB8, and CGB9, mapped to the 19q13.32 locus. This gene cluster also encompasses the CGB1 and CGB2 genes, which were originally considered to be pseudogenes, but as documented by several studies are transcriptionally active. Even though the protein products of these genes have not yet been identified, based on The Cancer Genome Atlas (TCGA) database analysis we showed that the mutual presence of CGB1 and CGB2 transcripts is a characteristic feature of cancers of different origin, including bladder urothelial carcinoma, cervical squamous cell carcinoma, esophageal carcinoma, head and neck squamous cell carcinoma, ovarian serous cystadenocarcinoma, lung squamous cell carcinoma, pancreatic adenocarcinoma, rectum adenocacinoma, testis germ cell tumors, thymoma, uterine corpus endometrial carcinoma and uterine carcinosarcoma.


2020 ◽  
Vol 14 (1) ◽  
pp. 53-63
Author(s):  
Shuai Li ◽  
Yue Teng ◽  
Min-Jie Yuan ◽  
Ting-Ting Ma ◽  
Jian Ma ◽  
...  

Aim: This study profiled differentially expressed long noncoding RNAs (lncRNAs) in lung squamous cell carcinoma (LSCC) to predict LSCC overall survival (OS) using The Cancer Genome Atlas data. Materials & methods: The RNA-seq and clinical dataset of 475 LSCC patients was retrieved from The Cancer Genome Atlas database and statistically analyzed. Results: There were 67 upregulated and 32 downregulated lncRNAs in LSCCs and 12 lncRNAs associated with OS. The seven-lncRNA signature was associated with poor OS and RP11-150O12.6 and CTA-384D8.35 were associated with better OS (p < 0.001). The seven lncRNAs-mRNA interaction network analysis showed their association with 187 protein-coding genes for cancer development, cell migration, adhesion, proliferation, apoptosis, angiogenesis and the MAPK signaling pathways. Conclusion: This seven-lncRNA signature is useful to predict LSCC OS.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4101 ◽  
Author(s):  
Sheng Yang ◽  
Jing Sui ◽  
Geyu Liang

Background Lung cancer is considered as one of the most frequent and deadly cancers with high mortality all around the world. It is critical to find new biomarkers for early diagnosis of lung cancer, especially lung squamous cell carcinoma (LUSC). The Cancer Genome Atlas (TCGA) is a database which provides both cancer and clinical information. This study is a comprehensive analysis of a novel diagnostic biomarker for LUSC, based on TCGA. Methods and Results The present study investigated LUSC-specific key microRNAs (miRNAs) from large-scale samples in TCGA. According to exclusion criteria and inclusion criteria, the expression profiles of miRNAs with related clinical information of 332 LUSC patients were obtained. Most aberrantly expressed miRNAs were identified between tumor and normal samples. Forty-two LUSC-specific intersection miRNAs (fold change >2, p < 0.05) were obtained by an integrative computational method, among them six miRNAs were found to be aberrantly expressed concerning characteristics of patients (gender, lymphatic metastasis, patient outcome assessment) through Student t-test. Five miRNAs correlated with overall survival (log-rank p < 0.05) were obtained through the univariate Cox proportional hazards regression model and Mantel–Haenszel test. Then, five miRNAs were randomly selected to validate the expression in 47 LUSC patient tissues using quantitative real-time polymerase chain reaction. The results showed that the test findings were consistent with the TCGA findings. Also, the diagnostic value of the specific key miRNAs was determined by areas under receiver operating characteristic curves. Finally, 577 interaction mRNAs as the targets of 42 LUSC-specific intersection miRNAs were selected for further bioinformatics analysis. Conclusion This study indicates that this novel microRNA expression signature may be a useful biomarker of the diagnosis for LUSC patients, based on bioinformatics analysis.


2021 ◽  
Author(s):  
Jiahuang Huang ◽  
Qinhui Zhang ◽  
Wei Li ◽  
Jianchang Shu

Abstract Background: ZCCHC24 is one of alternative splicing factors which affect immune cell infiltration, but the mechanisms whereby it drives immune infiltration in cancer remain uncertain. Methods: ZCCHC24 expression was analyzed via the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We evaluated the influence of ZCCHC24 on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between ZCCHC24 and cancer immune infiltrates was investigated via TIMER. In addition, correlations between ZCCHC24 expression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA.Results: ZCCHC24 significantly impacts the prognosis of diverse cancers via The Cancer Genome Atlas (TCGA). elevated ZCCHC24 expression was significantly correlated with poor OS and progression-free survival (PFS) in gastric cancers (OS HR = 2.11, P = 6.3e-12; PFS HR = 2.03, P = 3.1e-11). Moreover, ZCCHC24 significantly impacts the prognosis of diverse cancers via The Cancer Genome Atlas (TCGA). Specifically, high ZCCHC24 expression was correlated with worse OS and PFS in Stage, T stage, N stage, M stage, Lauren classification and differentiation of gastric cancer patients. ZCCHC24 expression was positively correlated with infiltrating levels of CD4+ T,CD8+ T cells, Macrophages, Neutrophils and dendritic cells (DCs) in stomach adenocarcinoma (STAD) and lung squamous cell carcinoma (LUSC). ZCCHC24 expression showed strong correlations with diverse immune marker sets in STAD and LUSC.Conclusions: These findings suggest that ZCCHC24 is a key factor which governs immune cell recruitment to gastric cancer and lung squamous cell carcinoma, potentially playing a vital role in governing immune cell infiltration and thus representing a valuable prognostic biomarker in gastric cancer and lung squamous cell carcinoma patients.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Hou ◽  
Yingbo Li ◽  
Ying Wang ◽  
Dongqiang Xu ◽  
Hailing Cui ◽  
...  

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N=514) and lung squamous cell carcinoma (LUSC) (N=502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p<0.001 and p=0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p=0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p<0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.


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