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RNA molecules and targeting microRNA (miRNA) have been reported as novel focuses in recent research on breast cancer. This study aimed to probe the expression of FOXO1 in the MDA-MB-231 cell line and to explore the target effects of FOXO1 with hsa-microRNA-204-5p (miR-204) on the biologic behavior of MDA-MB-231 cells. The expression of FOXO1 mRNA and protein in MDA-MB-231 cells were derived and verified from the public databases, literature, and experimental assays, then the downregulation of FOXO1 was confirmed in the MDA-MB-231 cell line. The target binding of FOXO1 and miR-204 was predicted by miRWalk and confirmed by luciferase reporter assays. MiR-204 targeted the 3' untranslated region of FOXO1 and reduced FOXO1 expression in miR-204-transfected cells, resulting in cell growth amplification but inhibition of cell migration and apoptosis, which were assessed using the MTT method, wound healing assays, and flow cytometry, respectively. The protein levels of serine-threonine kinase (AKT), c-jun N-terminal kinase (JNK), extracellular regulatory protein kinase (ERK), and the phosphorylated protein kinases (P-AKT, P-JNK, and P-ERK) were measured by western blot. It was found that AKT, JNK, and ERK remained constant, but P-AKT, P-JNK, and P-ERK were upregulated after miR-204 transfection. In summary, the expression of FOXO1 was downregulated in MDA-MB-231 cells; and the target binding of miR-204 and FOXO1 affected phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signal pathways, leading to different alterations of cellular activity in MDA-MB-231 cells., Competing Interests: None., (IJCEP Copyright © 2020.)

Breast cancer (BC) is a kind of malignant cancer that seriously threatens women's health. Research scientists have found that BC occurs as the result of multiple effects of the external environment and internal genetic changes. Cell cycle checkpoint kinase 1 (CHEK1) is a crucial speed limit point in the cell cycle. Alterations of CHEK1 have been found in various tumors but are rarely reported or verified in BC. By mining database information, a large amount of mRNA and protein data was collected and meta-analyzed. Also, in-house immunohistochemistry was carried out to validate the results of the CHEK1 expression levels. Relative clinical features of BC patients were calculated with the CHEK1 expression levels to determine their diagnostic value. The mRNA levels of CHEK1 were higher in 1,089 cases of BC tissues than in 291 cases of non-BC tissues. We observed that the mRNA levels of CHEK1 are related to the clinical stages of BC patients (P = 0.008) and are also significant for overall survival (HR = 1.6, P = 0.0081). Using the immunohistochemistry method, we calculated and confirmed, using Fisher's exact test (P < 0.001), that a high-level CHEK1 protein is exhibited in BC tissues. Overexpressed CHEK1 mRNA promotes the occurrence of BC. Also, up-regulated CHEK1 could serve as an independent risk biomarker in BC patients' prognoses., Competing Interests: None., (IJCEP Copyright © 2019.)

Growing evidence has revealed that the initiation of various malignancies is closely associated with alternative splicing (AS) events in certain key oncogenes. However, in diffuse large B-cell lymphoma (DLBCL), there is still a great deal to learn about AS variants. In this study, 33,724 AS variant profiles were obtained from 16,278 genes in 48 DLBCL cases. A total of 10 AS variants were identified as overall survival (OS)- related events via multivariate Cox regression analysis. Notably, alternative donor (AD) sites in AS events in the low-risk group showed a significantly better outcome in DLBCL patients than in the high-risk group (P=0.0002). The area under the curve (AUC) of the receiver-operator characteristic curve (ROC) for ADs in DLBCL was 0.746. Furthermore, 66 related splicing factors were obtained to investigate their potential correlations with AS events. Factors SF1, HNRNPC, HNRNPD, and HNRNPH3 were significantly involved in different OS-related AS variants. Collectively, we constructed valuable prognostic predictors for DLBCL patients and mapped novel splicing networks for further investigation of the underlying mechanisms related to AS variants in DLBCLs., Competing Interests: None.

Purpose: The aim of the present study is to promote deeper pathological and clinical understanding of gallbladder squamous cell carcinoma (GBSCC) and provide new evidence for its diagnosis and treatment., Methods: Two cases of GBSCC from the First Affiliated Hospital of Guangxi Medical University were collected. A comprehensive analysis was conducted based upon these 2 cases and another 119 GBSCC cases from the literature. Survival analysis was performed using the Kaplan-Meier method., Results: Among all the patients, GBSCC was frequently diagnosed in older women with a mean age of 62.8 years old. Abdominal pain was the most common symptom. The majority of GBSCC cases were combined with cholelithiasis. Keratinization was frequently observed microscopically. Among 90 cases with histology data, most showed high or, high-moderate differentiation (60%, 54/90). More cases were diagnosed in advanced TNM stages (85.4%, 82/96). In 73 cases, the follow-up time was 0.5-125 months, with a mean survival time 47.3 months and a median survival time of 12 months. Survival analysis indicated that patients with polypoid lesions (P = 0.047) and receiving R0 radical operation (P < 0.001) had better prognoses., Conclusion: Given the scarcity and implicit clinical manifestations of GBSCC, early diagnosis is challenging. The key to better survival is a radical operation with no remaining lesion., Competing Interests: None., (IJCEP Copyright © 2018.)

Objective: To explore potential targets and clinical value of miR-490-5p in the oncogenesis and progression of hepatocellular carcinoma (HCC)., Methods: Clinical value of miR-490-5p was accessed through The Cancer Genome Atlas (TCGA) and qRT-PCR analyses. Potential target mRNAs of miR-490-5p were predicted by bioinformatics methods and were annotated as Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, and Protein-Protein Interaction (PPI) network analysis., Results: miR-490 expression in HCC tissues was lower compared with normal control tissues based on TCGA and down regulation of miR-490-5p was verified by qRT-PCR (P<0.0001). Both miR-490 and miR-490-5p had moderate ability to diagnose HCC tissues from noncancerous tissues. Moreover, lower miR-490 level predicted poorer overall survival in patients with HCC (P=0.0063). One hundred and eighty-four mRNAs were selected as potential targets of miR-490-5p by overlap with 4,090 prediction genes and 1,478 differentially expressed genes (DEGs). Gene Ontology (GO) function analysis showed that the most significant terms were vasculature development, endoplasmic reticulum, and protein binding in biological process (BP), cellular component (CC), and molecular function (MF). In KEGG signaling pathway analysis, the statistically significant terms were lysosome, focal adhesion, glioma. In PPI network analysis, SRC, SRP9, PDGFRB, RPL28, and RPS23 were identified as the hub genes., Conclusion: miR-490-5p is down-regulated in HCC and may be a prospectively diagnostic and prognostic biomarker. Moreover, miR-490-5p might directly target SRC, SRP9, PDGFRB, RPL28, or RPS23 and play an important role in HCC., Competing Interests: None., (IJCEP Copyright © 2018.)

In this study, we investigated the levels of homeobox A13 (HOXA13) and the mechanisms underlying the co-expressed genes of HOXA13 in lung squamous cancer (LUSC), the signaling pathways in which the co-expressed genes of HOXA13 are involved and their functional roles in LUSC. The clinical significance of 23 paired LUSC tissues and adjacent non-tumor tissues were gathered. HOXA13 levels in LUSC were detected by quantitative real-time polymerase chain reaction (qRT-PCR). HOXA13 levels in LUSC from The Cancer Genome Atlas (TCGA) and Oncomine were analyzed. We performed receiver operator characteristic (ROC) curves of various clinicopathological features of LUSC. Co-expressed of HOXA13 were collected from MEM, cBioPortal and GEPIA. The functions and pathways of the most reliable overlapped genes were achieved from the Gene Otology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. The protein-protein interaction (PPI) networks were mapped using STRING. HOXA13 in LUSC were markedly upregulated compared with those in the non-cancerous controls as demonstrated by qRT-PCR (LUSC: 0.330±0.360; CONTROLS: 0.155±0.142; P =0.021). TCGA (LUSC: 6.388±2.097, CONTROLS: 1.157±0.719; P <0.001) and Hou's study from Oncomine (LUSC: 1.154±0.260; CONTROLS: 0.957±0.065; P =0.001) showed the same tendency. Meanwhile, the area under the curve (AUC) of TNM was calculated as 0.877 with P =0.002. Based on the HOXA13 expression data from TCGA, the ROC of the tissue types was calculated as AUC=0.971 ( P <0.001). In addition, 506 genes were filtered as co-expression genes of HOXA13. The 3 most significant KEGG pathways were metabolic pathways ( P =5.41E-15), the calcium signaling pathway ( P =3.01E-11), and the cAMP signaling pathway ( P =5.63E-11). MAPK1, GNG7, GNG12, PRKCA were selected as the hub genes. In conclusion, HOXA13 was upregulated and related to the TNM stage in LUSC. The expression of hub genes in LUSC might be deregulated by HOXA13. Moreover, the 4 co-expressed hub genes of HOXA13 might be crucial biomarkers for the diagnosis and prognosis of LUSC, as well as the development of novel therapeutic targets against LUSC., Competing Interests: None., (IJCEP Copyright © 2017.)

The aberrant expression of mitotic arrest deficient 2-like 1 (MAD2L1) has been found to promote tumor formation by inducing chromosomal instability and aneuploidy in cells. In breast cancer (BRCA), limited studies have been focused on MAD2L1 expression and its impact on tumor progression. Thus, we conducted this study to comprehensively analyze MAD2L1 expression and its clinicopathological significance as well as diagnostic value for BRCA. Immunohistochemistry was performed with the 209 invasive ductal BRCA samples and the corresponding adjacent tissues to investigate MAD2L1 expression in BRCA and its relationship between clinicopathological features of BRCA. Then, the clinicopathological role of MAD2L1 was confirmed by RNA-sequencing or microarray data from the Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO). Particularly, summarized receiver operating characteristic (SROC) curve was plotted to explore the diagnostic capacity of MAD2L1 in BRCA. The results showed that MAD2L1 presented overexpression in BRCA and was significantly associated with higher clinical stage and histological grade of BRCA. A significant correlation was also found between MAD2L1 expression and several tumor indicators including ER, P53, HER-2 and Ki-67. Moreover, area under curve (AUC) value (0.9642) from SROC revealed potential diagnostic value of MAD2L1 for BRCA. In summary, MAD2L1 may be involved in the occurrence and development of BRCA and MAD2L1 detection could improve the diagnosis and prognostic evaluation of BRCA., Competing Interests: None., (IJCEP Copyright © 2017.)

Invasive cribriform carcinoma (ICC) is a rare type of invasive breast cancer. We aim to investigate the clinicopathological features, immunophenotypes, diagnosis and differential diagnosis of ICC. Thus, clinicopathological data of 12 ICC patients were collected. All 12 cases were female, aged 38 to 75 years, with a median age of 53 years old. The maximum diameter of the tumor was 2 cm to 10 cm, in which the median tumor size was 2.54 cm in pure ICC and classical ICC. Microscopically, the cancer nests of ICC assumed an invasive, irregular island-shaped distribution, with an irregular mesh structure internally and fibrous reactions around most cancer nests. 67% (8/12) of cases were grade 1 and 33% (4/12) of cases were grade 2 tumors. Immunohistochemically, ER and PR were moderately to strongly positive with the positive tumor cell number accounting for 30% to 95% in all cases. HER-2 was negative in all cases except in one case which was positive (2+). Myoepithelial markers such as Calponin, p63, CK5/6 and CD10 were all negative in the cancer nests. 58% (7/12) of cases had a ki67 index of ≤ 14%. All follow-up patients were followed for 12 to 70 months (with a mean of 42 months), and were disease-free after treatment except for one patient whom we lost during the follow up. In conclusion, ICC, as a special type of breast cancer, has its unique clinicopathological and immunophenotypic characteristics, leading to a good prognosis., Competing Interests: None., (IJCEP Copyright © 2017.)

MicroRNAs (miRNAs) are involved in the pathogenesis of diverse types of malignancies, including hepatocellular carcinoma (HCC). However, miR-365 has rarely been reported in HCC. The purpose of the current study was to identify the clinical relevance of miR-365 in HCC and examine the potential downstream signaling effectors.Using real-time RT-qPCR, we confirmed that miR-365 expression was markedly decreased in HCC tissues (3.5138 ± 2.2527) compared to that in paraneoplastic liver tissues (6.5950 ± 4.1230, P<0.001). Receiver operating characteristic curves to assess the diagnostic value of miR-365 in HCC demonstrated that the area under the curve was 0.757. Furthermore, down-regulation of miR-365 was remarkably correlated to the number of tumor nodes, status of metastasis, clinical TNM stage, portal vein tumor embolus and vaso-invasion. In addition to the clinical value of miR-365, a total of 238 downstream direct targets selected by online predictive algorithms and key genes generated from natural language processing and the Cancer Genome Atlas (TCGA) were pooled for bioinformatics analysis. These potential targets were mainly enriched in the Ras Pathway using PANTHER analysis and the 'Pathways in Cancer' using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In conclusion, down-regulated miR-365 may contribute to the progression and metastasis of HCC via targeting multiple signaling pathways, and miR-365 may act as a novel biomarker for HCC., Competing Interests: None., (IJCEP Copyright © 2017.)

Background: MiR-101-3p has been reported to suppress invasion and metastasis in hepatocellular carcinoma (HCC) cells. However, the relevant mechanisms are still unclear. The research seeks to determine systematic value of miR-101-3p in HCC, and comprehensively summarize the predicted target genes as well as their potential function, pathways and networks in HCC., Methods: The miR-101-1 profiles in 353 HCC patients from The Cancer Genome Atlas (TCGA) were analyzed. Meta-analysis was performed to estimate relationship of miR-101 (including precursor and mature miR-101) with clinical features and prognosis in HCC. Further, the promising targets of miR-101-3p were predicted and followed with Gene Ontology (GO), pathway and network analysis. In addition, the functional impact of miR-101-3p was confirmed with in vitro experiments in HCC cells., Results: In TCGA data, low-expression of miR-101-1 might be a diagnostic (AUC: 0.924, 95% CI: 0.894-0.953) and prognostic (HR=1.55) marker for HCC. Down-regulated miR-101-1 also correlated with poor differentiation, advanced TNM stage, lymph node metastasis and high AFP level of HCC. Meta-analysis revealed that miR-101 down-regulation were associated with poor prognosis, high AFP level and advanced TNM stage of HCC. Moreover, 343 hub genes were filtered and miR-101-3p may be involved in intracellular signaling cascade, transcription, metabolism and cell proliferation. Focal adhesion and pathways in cancer were also significantly enriched. In vitro experiments demonstrated that miR-101-3p inhibited proliferation and promoted apoptosis in HCC cells., Conclusions: MiR-101-1 may be a prospective biomarker for diagnosis and prognosis of HCC. Potential targets of miR-101-3p could regulate genesis and development of HCC. The data offers insights into biological significances and promising targets of miR-101-3p for further investigation and potential therapies in HCC., Competing Interests: None.