scholarly journals microRNA-23a in Human Cancer: Its Roles, Mechanisms and Therapeutic Relevance

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 7 ◽  
Author(s):  
Ning Wang ◽  
Hor-Yue Tan ◽  
Yi-Gang Feng ◽  
Cheng Zhang ◽  
Feiyu Chen ◽  
...  

microRNA-23a (miR-23a) is one of the most extensively studied miRNAs in different types of human cancer, and plays various roles in the initiation, progression, and treatment of tumors. Here, we comprehensively summarize and discuss the recent findings about the role of miR-23a in cancer. The differential expression of tissue miR-23a was reported, potentially indicating cancer stages, angiogenesis, and metastasis. miR-23a in human biofluid, such as plasma and salivary fluid, may be a sensitive and specific marker for early diagnosis of cancer. Tissue and circulating miR-23a serves as a prognostic factor for cancer patient survival, as well as a predictive factor for response to anti-tumor treatment. The direct and indirect regulation of miR-23a on multiple gene expression and signaling transduction mediates carcinogenesis, tumor proliferation, survival, cell migration and invasion, as well as the response to anti-tumor treatment. Tumor cell-derived miR-23a regulates the microenvironment of human cancer through manipulating both immune function and tumor vascular development. Several transcriptional and epigenetic factors may contribute to the dysregulation of miR-23a in cancer. This evidence highlights the essential role of miR-23a in the application of cancer diagnosis, prognosis, and treatment.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14519-e14519
Author(s):  
Hanbyoul Cho ◽  
Gwan Hee Han ◽  
Doo Byung Chay ◽  
Jaehoon Kim

e14519 Background: Transcriptional factor FOXO1and PAX3 has been reported to play an imported role in human cancer, but the role in cervical cancer has not yet been clarified. Here, we evaluated the functional role of FOXO1 with cervical cancer cells and the expression together with clinical significance of FOXO1 and PAX3 among cervical lesions was investigated. Methods: In vitro assessment of cell functions by cell viably assay, cell migration and invasion assay was evaluated using FOXO1 knockdown cervical cancer cell lines. Immuno-histochemical (IHC) staining analyses of FOXO1 and PAX3 were performed with tissue microarray (TMA) consisting of 209 cervical cancers, 366 high grade cervical intraepithelial neoplasias (CIN), 130 low grade CIN and 328 matched nonadjacent normal cervical epithelial tissues. The clinical significance was investigated by comparing the data with various clinicopathologic characteristics, including survival in cervical cancer. Results: In vitro result revealed that knockdown of FOXO1 was associated decreased cell viability ( p< 0.001), migration ( p< 0.001) and invasion ( p< 0.05) supporting the oncogenic role of FOXO1 in cervical cancer. FOXO1 and PAX3 expression was significantly higher in CIN (both p< 0.001) and cancer tissue (both p< 0.001) than in normal tissue. FOXO1 expression showed significant correlation with PAX3 (Spearman’s rho = 0.377, p< 0.001) in a cervical cancer. Multivariate analysis indicates that FOXO1 expression (hazard ratio = 4.01 [95% CI, 1.22–13.10], p= 0.021) and advanced FIGO stage (hazard ratio = 3.89 [95% CI, 1.35–11.19], p= 0.012) were independent prognostic factor on overall survival. Conclusions: This study reveals the association between FOXO1 and PAX3 expression with clinicopathologic variables, including survival of cervical cancer patients. Our results not only suggest the promising potential of FOXO1 as a prognostic and survival marker, but also warrant further studies on a possible link between the biological function of FOXO1 and the pathogenesis of cervical cancer.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii24-iii24
Author(s):  
Q Chang ◽  
L Zhu ◽  
N Li

Abstract BACKGROUND Medulloblastoma (MB) is the most common malignant paediatric brain tumor. Recent studies show that M2 cells were relative more abundant in Shh subtype of MBs compared with other three subtypes. It’s known that M2 cells have close relationship with many tumors’ progression. But if they play any role in the progression of Shh subtype of MB is not yet clear. Many studies demonstrate that exosomes carring miRNAs have close relationship with tumor invasion. The aim of present study is to clarify the role of exosome miRNA between tumor cells and microglias during the progression of Shh subtype of medulloblastoma. MATERIAL AND METHODS Immunofluerescence staining using iNOS and Arg1, which is M1 and M2 specific marker, respectively, was performed in four subtypes of MBs. After coculture of exosomes extracted from Shh subtype of MB cell (DAOY) with microglia cell (BV2), Q-PCR and ELISA assay were done to evaluate the polarization status of the microglia. Transwell and scratch assay were then performed to detect the migration ability of DAOY cell after treatment of exosomes from polirized M2 cells. MiRNA sequencing by Ion Proton technology was then done to analyze the miRNAs expression level between Shh subtype and other subtype of MBs. Transformation assay was used to overexpress and inhibit the expression of these miRNAs respectively to further clarify the role of exosome miRNA in the polarization of BV2 cells. RESULTS M2 cells were observed more abundant than other three subtypes of tumors, supporting that M2 cells play some role in this subtype of MBs. Exosomes of DAOY cells can induce the polarization of M2 cells. The polarized M2 cells can improved the migration and invasion ability of DAOY cell. Dozens of miRNAs were identified with different expression level between Shh subtype of MBs and other subtype of MB cells. Among them, 4 miRNAs were reported to be related with polariztion of M2 in many other lesions. Three of the 4 miRNAs can induce the polarization of M2 in present study. CONCLUSION Our study demonstrated exosome miRNA play a critical role between tumor cells and microglias during the progression of Shh subtype of medulloblastoma.


The Analyst ◽  
2019 ◽  
Vol 144 (18) ◽  
pp. 5504-5510 ◽  
Author(s):  
Fei Yin ◽  
Liqi Liu ◽  
Xia Sun ◽  
Laiyong Hou ◽  
Yu Lu ◽  
...  

Simultaneous detection of different types of cancer biomarkers (nucleic acids and proteins) could facilitate early diagnosis of cancer and clinical treatment.


2019 ◽  
Vol 18 ◽  
pp. 153303381989225 ◽  
Author(s):  
Zhe Quan ◽  
Bei-bei Zhang ◽  
Fang Yin ◽  
Jiru Du ◽  
Yuan-ting Zhi ◽  
...  

Basal cell carcinoma is driven by the aberrant activation of hedgehog signaling. DEAD (Asp-Glu-Ala-Asp) box protein 5 is frequently overexpressed in human cancer cells and associated with the tumor growth and invasion. The purpose of this study was to investigate the role of DEAD (Asp-Glu-Ala-Asp) box protein 5 in the growth, migration, and invasion of basal cell carcinoma. The role of DEAD (Asp-Glu-Ala-Asp) box protein 5 was detected by quantitative real-time polymerase chain reaction, Western blot, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay in basal cell carcinoma cells. The associations between JAK2/STAT3 pathway and DEAD (Asp-Glu-Ala-Asp) box protein 5 were analyzed in basal cell carcinoma cells. Results showed that DEAD (Asp-Glu-Ala-Asp) box protein 5 is overexpressed in basal cell carcinoma cells. DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown inhibited the migration and invasion of basal cell carcinoma cells. DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown increased the apoptosis of basal cell carcinoma cells induced by tunicamycin. Results found that DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown increased JAK2 and STAT3 expression in basal cell carcinoma cells. JAK2 inhibitor decreased STAT3 expression and abolished the inhibitory effects of DEAD (Asp-Glu-Ala-Asp) box protein 5 silencing on migration and invasion in basal cell carcinoma cells. In conclusion, these results indicate that DEAD (Asp-Glu-Ala-Asp) box protein 5 is a potential target for inhibiting basal cell carcinoma cells growth, migration, and invasion by downregulating JAK2/STAT3 pathway.


2020 ◽  
Vol 9 (1) ◽  
pp. 3-13
Author(s):  
Nguyen Hoang Danh ◽  
Thieu Hong Hue ◽  
Quang Trong Minh ◽  
K' Trong Nghia ◽  
Nguyen Thanh Tung ◽  
...  

miRNA (microRNA) are short RNA molecules in length from 20 to 24 nucleotides that have been shown to play an important role in regulating gene expression in many different types of human cancer. Meanwhile, miRNA-214 is one of the known miRNAs involved in the formation of nasopharyngeal carcinoma (NPC) through overexpression that promotes proliferation and development of cancer cells. However, in Vietnam, the study of miR-214 related to NPC has not been conducted yet. With the aims to develop the further studies of miR-214 on NPC in Vietnamese patients, in this initial study, we conducted the analysis of miR-214 expression in previous publications, as well as the prediction of miR-214 potential target genes, which involved in many cellular pathways. Here we applied bioinformatics tools to predict miRNAs and their targets, and discuss the role of miR-214 in the context of human cancers. As the results, miR-214 acted as the oncogenic roles in NPC, relevanted to many pathways, such as cell proliferation, apoptosis, metastasis and invasion through the its target genes LTF, Bim, Bax, LINC0086, etc. In conclusion, the use of computional approaches facilitate the further experimental validation of miRNAs in general, particularly miR-214, in Vietnamese NPC patients.


2020 ◽  
Vol 10 (6-s) ◽  
pp. 183-185
Author(s):  
Rajashri Champanery ◽  
Drashti Joshi

The tumor suppressor TP53 gene is one of the most frequently mutated in different types of human cancer. Particularly in colorectal cancer (CRC), it is believed that TP53 mutations play a role in the adenoma-carcinoma transition of tumors during pathological process. The TP53 mutation is the key step driving the transition from adenoma to adenocarcinoma. The functional roles of TP53 mutation in tumor development have been comprehensively investigated. In this mini review, we comprehensively summarize the p53 mutants in CRC progression and discuss the current strategies for p53 mutants in malignancies. Keywords: p53 mutants, colorectal cancer, Tp53 mutation


Author(s):  
Yujing Wang ◽  
Jing Wang ◽  
Chunmei Liu ◽  
Min Li

SIRT1 (silent information regulator 1), a NAD+-dependent III class histone deacetylase, plays crucial roles in cell proliferation, apoptosis, senescence, metabolism, and stress responses. Nevertheless, the role of SIRT1 in tumorigenesis remains unclear. In the present study, we measured expression levels of SIRT1 and HPV16 E7 protein in cervical cancer tissue and calculated their correlations. We measured the effect of silencing SIRT1 on the proliferation, migration, invasion, and apoptosis in human cervical cancer SiHa cells. Immunohistochemistry results revealed that the expression of SIRT1 was upregulated with progression from CINII-III to cervical cancer, but was not expressed in normal cervical tissues and CINI. There was a positive correlation between SIRT1 expression and HPV16 E7 expression in cervical cancer tissues, and silencing of HPV16 E7 downregulated the expression of SIRT1. Depletion of SIRT1 significantly downregulated SIRT1 expression, and inhibited proliferation, migration, and invasion of SiHa cells, inducing apoptosis. Taken together, the data suggest that SIRT1 promotes cervical cancer carcinogenesis. SIRT1 inhibition is a potential treatment strategy for cervical cancer.


Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 629
Author(s):  
Anna Perri ◽  
Vittoria Rago ◽  
Rocco Malivindi ◽  
Lorenza Maltese ◽  
Danilo Lofaro ◽  
...  

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs.


2020 ◽  
Author(s):  
Zhijian Wei ◽  
Lixiang Zhang ◽  
Angqing Li ◽  
Chuanhong Li ◽  
Wenxiu Han ◽  
...  

Abstract Gastric cancer (GC) is one of the deadliest cancers in China. And, it can be regulated by MicroRNAs (miRNAs) generally. miR-491-5p function as a tumor suppressor in different types of cancer, but we still don’t know the role of miR-491-5p in gastric cancer. In this study, we found that high level of miR-491-5p caused a weak cell proliferation, migration and invasion abilities. In order to explore the role of miR-491-5p in vivo, we set a xenograft mouse model, and also found that high level of miR-491-5p suppressed tumor growth. Moreover, we found that miR-491-5p regulate the tumor development thought regulate the expression of EMT, cell adhesion genes and IFITM2. These data show that miR-491-5p function as a tumor suppressor in GC both in vitro and in vivo .


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