Cancer Biomarkers - Volume 30, issue 3

Authors: Li, Shujing | Zhang, Yanyan | Dong, Jian | Li, Ruihuan | Yu, Bo | Zhao, Wenjun | Liu, Jing

Article Type: Research Article

Abstract: Long non-coding RNAs (lncRNAs) are important to the occurrence and advancement of human cancers. We found through GEPIA that LINC00893 was lowly expressed in thyroid carcinoma (THCA) tissues, whereas the specific functions of LINC00893 has never been reported in PTC. In the current study, we confirmed that LINC00893 was expressed at a low level in PTC cells. Through gain-of-function assays, we determined that LINC00893 overexpression abrogated proliferation and migration abilities of PTC cells. Through signal transduction reporter array we found that LINC00893 potentially modulated the signals of phosphatase and tensin homolog (PTEN)/AKT pathway. In addition, overexpression of LINC00893 increased the …expression of PTEN but reduced the levels of phosphorylated AKT in PTC. Additionally, mechanism assays unveiled that LINC00893 stabilized PTEN mRNA via recruiting Fused in sarcoma (FUS) protein. Finally, rescue assays demonstrated that LINC00893 hampered the proliferation and migration of PTC cells via PTEN/AKT pathway. Together, our study first clarified that LINC00893 functions as a tumor suppressor in PTC by blocking AKT pathway through PTEN upregulation. Show more

Keywords: LINC00893, papillary thyroid cancer, FUS, PTEN/AKT pathway

DOI: 10.3233/CBM-190543

Citation: Cancer Biomarkers, vol. 30, no. 3, pp. 277-286, 2021

Authors: Ni, Ming | Yan, Qin | Xue, Hui | Du, Yanfang | Zhao, Shuangdan | Zhao, Zhiming

Article Type: Research Article

Abstract: BACKGROUND: The dysregulation of microRNA-802 (miR-802) has crucial roles in cancer progression. Nevertheless, the bio-function of miR-802 in cervical cancer remains unclear. OBJECTIVE: Hence, we illuminated the potential roles of miR-802 in cervical cancer cell growth, migration, and invasion. METHODS: The levels of miR-802 and myosin regulatory light chain interacting protein (MYLIP) were measured using qRT-PCR assay. The potential effects of miRNA-802 on cervical cancer cell proliferation and metastatic phenotypes were determined using CCK-8, colony formation, wound healing and Transwell invasion assays. MYLIP was validated as a downstream target gene of miRNA-802 using …bioinformatics analysis tool and luciferase report gene assay. The impact of miR-802 on the growth of cervical cancer cell in vivo was analyzed using xenograft model. The expression of MYLIP was measured by western blotting and immunohistochemistry (IHC). RESULTS: MiRNA-802 was distinctly down-regulated in cervical cancer cells as well as clinical cervical cancer samples. Upregulation of miRNA-802 significantly inhibited the growth and aggressiveness of cervical cancer cell. Additional, MYLIP was a functional target of miR-802. MYLIP was ovrerexpressed in cervical cancer and MYLIP level was negatively associated with the level of miR-802. Overexpression of MYLIP eliminated the inhibitory effects of miR-802 on growth and metastatic-related traits of cervical cancer cell. In vivo , miR-802 also markedly reduced the tumor growth of cervical cancer cell and decreased the expression of MYLIP. CONCLUSIONS: MiR-802 inhibits the growth and metastatic-related phenotypes of cervical cancer cell through targeting MYLIP. Show more

Keywords: Cervical cancer, miR-802, MYLIP, invasion, metastasis

DOI: 10.3233/CBM-201523

Citation: Cancer Biomarkers, vol. 30, no. 3, pp. 287-298, 2021

Authors: Gong, Zhaohua | Chu, Hongjin | Chen, Jian | Jiang, Lixin | Gong, Benjiao | Zhu, Peng | Zhang, Chenglin | Wang, Zhixin | Zhang, Wendi | Wang, Jiahui | Li, Chen | Zhao, Huishan

Article Type: Research Article

Abstract: BACKGROUND: Previous studies revealed that DEP domain containing 1 (DEPDC1) is involved in the carcinogenesis and progression of several types of human cancer. However the role of DEPDC1 in gastric cancer has not been studied. OBJECTIVE: The objective of this study was to study the expression and pathophysiological function of DEPDC1 in gastric cancer. METHODS: DEPDC1 expression in gastric adenocarcinoma cells was examined with Western blot and qRT-PCR. Clinical pathological features of patients were determined by immunohistochemistry. The effect of DEPDC1 expression on cell proliferation was studied by in vitro cell proliferation assay; …and cell cycle influence was assessed by flow cytometry. Survival curves were plotted using Kaplan-Meier. RESULTS: DEPDC1 was overexpressed in gastric adenocarcinoma tissues compared with the paired adjacent normal gastric tissues, in accordance with mRNA level downloaded from GEPIA database. DEPDC1 expression level was significantly associated with cancer metastasis and differentiation. DEPDC1 upregulation caused cell cycle accelerating from G1 to S phase, and it was correlated with poorer overall survival. CONCLUSION: Therefore, DEPDC1 upregulation in gastric adenocarcinoma is associated with tumor development and poor clinical outcomes of the patients, implying DEPDC1 might be a potential therapeutic target against gastric cancer. Show more

Keywords: DEPDC1, gastric cancer, proliferation, TCGA

DOI: 10.3233/CBM-201760

Citation: Cancer Biomarkers, vol. 30, no. 3, pp. 299-307, 2021

Authors: Liu, Zhining | Gu, Yimei | Cheng, Xiaohu | Jiang, Heng | Huang, Yang | Zhang, Yingfeng | Yu, Gang | Cheng, Yunsheng | Zhou, Lianbang

Article Type: Research Article

Abstract: Colorectal cancer is a major public health problem and fourth guiding cause of cancer-induced mortality worldwide. The five-year survival rate for patients with colorectal cancer remains poor, and almost half of colorectal cancer patients present recurrence and die within five years. The increasing studies showed that long non-coding RNA (lncRNA) was involved in colorectal cancer. Therefore, this study was used to explore molecular mechanisms of nuclear paraspeckle assembly transcript 1 (NEAT1) in colorectal cancer. The real-time quantitative polymerase chain reaction (RT-qPCR) was employed to estimate the expression levels of NEAT1, Nuclear receptor 4 A1 (NR4A1), and miR-486-5p in colorectal cancer …tissues and cells. Kaplan-Meier curve was conducted to analyze relationship between survival time of colorectal cancer patients and level of NEAT1. The protein levels of NR4A1, β -catenin, c-Myc, and cyclinD1 were assessed with western blot assay. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays were performed to evaluate proliferation and apoptosis of colorectal cancer cells, respectively. The migration and invasion abilities of cells were examined by transwell assay. The relationship between miR-486-5p and NEAT1 or NR4A1 was confirmed by dual-luciferase reporter assay. We found NEAT1 and NR4A1 were highly expressed in colorectal cancer tissues and cell lines compared with controls. Loss-functional experiments revealed that knockdown of NEAT1 or NR4A1 repressed proliferation and motility, while inducing apoptosis of colorectal cancer cells. The gain of NR4A1 could abolish NEAT1 silencing-induced effects in colorectal cancer cells. In addition, NEAT1 contributed to colorectal cancer progression through mediating NR4A1/Wnt/β -catenin signaling pathway. In conclusion, NEAT1 stimulated colorectal cancer progression via acting as competing endogenous RNA to sponge miR-486-5p and regulate NR4A1/Wnt/β -catenin signaling pathway. Show more

Keywords: LncRNA NEAT1, miR-486-5p, NR4A1/Wnt/β-catenin, colorectal cancer

DOI: 10.3233/CBM-201733

Citation: Cancer Biomarkers, vol. 30, no. 3, pp. 309-319, 2021

Authors: Wang, Guanghui | Bie, Fenglong | Li, Guangxu | Shi, Junping | Zeng, Yanwu | Du, Jiajun

Article Type: Research Article

Abstract: BACKGROUND: Metastasis regularly is a marker of the disease development of cancers. Some metastatic sites significantly showed more serious clinical outcomes in non-small cell lung cancer (NSCLC). Whether they are caused by tissue-specific (TS) or non-tissue-specific (NTS) mechanisms is still unclear. OBJECTIVE: Explore co-expression gene modules of non-small cell lung cancer metastases. METHODS: Weighted Correlation Network Analysis (WGCNA) was used to identify the gene modules among the metastases of NSCLC. The clinical significance of those gene modules was evaluated with the Cox hazard proportional model with another independent dataset. Functions of each gene …module were analyzed with gene ontology. Typical genes were further studied. RESULTS: There were two TS gene modules and two NTS gene modules identified. One TS gene module (green module) and one NTS gene module (purple module) significantly correlated with survival. This NTS gene module (purple module) was significantly enriched in the epithelial-to-mesenchymal transition (EMT) process. Higher expression of the typical genes (CA14, SOX10, TWIST1, and ALX1) from EMT process was significantly associated with a worse survival. CONCLUSION: The lethality of NSCLC metastases was caused by TS gene modules and NTS gene modules, among which the EMT-related gene module was critical for a worse clinical outcome. Show more

Keywords: Non-small cell lung cancer, metastases, gene module, weighted correlation network analysis, co-expression

DOI: 10.3233/CBM-201605

Citation: Cancer Biomarkers, vol. 30, no. 3, pp. 321-329, 2021

Authors: Yu, Jiangqing | Du, Fen | Yang, Liping | Chen, Ling | He, Yuanxiang | Geng, Ruijin | Wu, Le | Xie, Baogang

Article Type: Research Article

Abstract: BACKGROUND: Histological subtypes of lung cancer are crucial for making treatment decisions. However, multi-subtype classifications including adenocarcinoma (AC), squamous cell carcinoma (SqCC) and small cell carcinoma (SCLC) were rare in the previous studies. This study aimed at identifying and screening potential serum biomarkers for the simultaneous classification of AC, SqCC and SCLC. PATIENTS AND METHODS: A total of 143 serum samples of AC, SqCC and SCLC were analyzed by 1 HNMR and UPLC-MS/MS. The stepwise discriminant analysis (DA) and multilayer perceptron (MLP) were employed to screen the most efficient combinations of markers …for classification. RESULTS: The results of non-targeted metabolomics analysis showed that the changes of metabolites of choline, lipid or amino acid might contribute to the classification of lung cancer subtypes. 17 metabolites in those pathways were further quantified by UPLC-MS/MS. DA screened out that serum xanthine, S-adenosyl methionine (SAM), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) contributed significantly to the classification of AC, SqCC and SCLC. The average accuracy of 92.3% and the area under the receiver operating characteristic curve of 0.97 would be achieved by MLP model when a combination of those five variables as input parameters. CONCLUSION: Our findings suggested that metabolomics was helpful in screening potential serum markers for lung cancer classification. The MLP model established can be used for the simultaneous diagnosis of AC, SqCC and SCLC with high accuracy, which is worthy of further study. Show more

Keywords: Subtypes of lung cancer classification, serum biomarkers, metabolomics, 1H-NMR, UPLC-MS/MS

DOI: 10.3233/CBM-201440

Citation: Cancer Biomarkers, vol. 30, no. 3, pp. 331-342, 2021

Authors: Kalantzakos, Thomas J. | Sullivan, Travis B. | Sebel, Luke E. | Canes, David | Burks, Eric J. | Moinzadeh, Alireza | Rieger-Christ, Kimberly M.

Article Type: Research Article

Abstract: BACKGROUND: MicroRNAs (miRNAs), a group of non-coding post-transcriptional regulators of gene expression, are dysregulated in clear cell renal cell carcinoma (ccRCC) and play an important role in carcinogenesis. Our prior work identified a subset of miRNAs in pT1 ccRCC tumors associated with progression to metastatic disease. OBJECTIVE: To investigate the impact of two of these dysregulated miRNA, miR-15a-5p and -26a-5p, in an effort to elucidate the mechanisms underpinning aggressive forms of stage I ccRCC. METHODS: The ccRCC cell line 786-O was transfected with pre-miRs-15a-5p and -26a-5p to rescue expression. Cell proliferation was measured …via MT Cell Viability Assay. O-GlcNAc-transferase (OGT), a known protein in ccRCC proliferation, was identified by bioinformatics analysis as a target of both miRNA and validated via luciferase reporter assay to confirm binding of each miR to the 3 ′ untranslated region (UTR). OGT protein expression was evaluated via western blotting. RESULTS: Luciferase assay confirmed specificity of miR-15a-5p and -26a-5p for the OGT UTR. Western blot analysis for OGT showed reduced expression following co-transfection of both miRNAs compared to negative control or individual transfection. Co-transfection of these miRNAs greatly reduced proliferation when compared to negative control or the individual transfections. CONCLUSION: Our results indicate that the dysregulation of miR-15a-5p and -26a-5p contribute cooperatively to the proliferation of ccRCC through their regulation of OGT. These results give insight into the pathogenesis of aggressive early stage ccRCC and suggest potential therapeutic targets for future research. Show more

Keywords: Biomarkers, clear cell renal cell cancer (ccRCC), microRNA, O-GlcNAc-transferase (OGT), proliferation

DOI: 10.3233/CBM-200553

Citation: Cancer Biomarkers, vol. 30, no. 3, pp. 343-351, 2021

Article Type: Correction

DOI: 10.3233/CBM-210951

Citation: Cancer Biomarkers, vol. 30, no. 3, pp. 353-, 2021