miR‐181a mediates <scp>TGF</scp>‐β‐induced hepatocyte <scp>EMT</scp> and is dysregulated in cirrhosis and hepatocellular cancer

Brockhausen, Jennifer; Tay, Szun S.; Grzelak, Candice Alexandra; Bertolino, Patrick; Bowen, David G.; d’Avigdor, W.; Teoh, Narcissus; Pok, Sharon; Shackel, Nicholas; Gamble, Jennifer R.; Vadas, Mathew A.; McCaughan, Geoffrey W.

doi:10.1111/liv.12517

Cited by 72 publications

(59 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MicroRNAs are critical to both physiological and pathological processes, including tumor development and progression [7,9,25]. Some miRNAs have even been identified as cancer markers or prognostic markers for cancer patients [9,10,26].…”

Section: Discussionmentioning

confidence: 99%

miR-744 is a potential prognostic marker in patients with hepatocellular carcinoma

Tan

Bai

Zou

et al. 2015

Clinics and Research in Hepatology and Gastroenterology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

miR-744 is a potential prognostic marker in patients with hepatocellular carcinoma

Tan

Bai

Zou

et al. 2015

Clinics and Research in Hepatology and Gastroenterology

View full text Add to dashboard Cite

“…HCC develops predominantly in an established background of chronic liver diseases mainly caused by persistent infection of hepatitis B [4] and/or hepatitis C virus, alcoholic liver disease, or non-alcoholic steatohepatitis [5,6]. Meanwhile, growing evidence indicates that the epithelial-mesenchymal transition (EMT), a developmental process by which epithelial cells reduce intercellular adhesions and acquire fibroblastoid properties, has important roles in the acquisition of the invasive and metastatic potentials of cancer progression [7,8,9,10]. We have recently reported that sorafenib [11,12] exerts a potent inhibitory activity against the EMT by inhibiting MAPK signaling and SNAI1 expression in HCC [13].…”

Section: Introductionmentioning

confidence: 99%

Impact of Tight Junction Protein ZO-1 and TWIST Expression on Postoperative Survival of Patients with Hepatocellular Carcinoma

Nagai¹,

Arao²,

Nishio³

et al. 2016

Dig Dis

View full text Add to dashboard Cite

Background: Epithelial-mesenchymal transition (EMT) is considered to play a critical role in cancer progression and metastasis. However, the impact of EMT on the prognosis of hepatocellular carcinoma (HCC) is still elusive. In this study, we examined the relationship between the expression of EMT markers and recurrence-free survival (RFS) and overall survival (OS) in HCC patients after hepatic resection. Summary: The mRNA expression of 15 genes related to EMT was assessed by quantitative real-time polymerase chain reaction in cancerous tissues from 72 patients who underwent hepatic resection of HCC between January 2005 and December 2010 at our hospital. The upregulation of TWIST and the downregulation of tight junction protein ZO-1 (TJP1) were significantly associated with shorter RFS as well as OS. Increased levels of TWIST and decreased levels of TJP1 should be predictive markers for poor prognosis in patients with HCC after hepatectomy; those could serve as potential biomarkers for the treatment of HCC. Key Messages: A low level of TJP1 and high level of TWIST expression were prognostic factors predicting HCC after hepatic resection.

show abstract

“…As in glioblastoma, significant downregulation of hsa-miR-181a was also observed in squamous lung cell carcinoma,83 oral squamous cell carcinoma,71 luminal A-like breast cancer,67 and non-small-cell lung cancer 84. However, hsa-miR-181a was significantly overexpressed in MCF-7 breast cancer cells,85 colorectal cancer,28 and hepatocellular carcinoma cells 56,86,87. Hsa-miR-181a was upregulated in acute myeloid leukemia,76 especially in the M1 and M2 subtypes, and in myelodysplastic syndromes88 but downregulated in multiple myeloma89 and chronic lymphocyte leukemia 79,90.…”

Section: Discussionmentioning

confidence: 92%

“…Thus, tissue-specific miRNAs may be used as effective biomarkers for cancer diagnosis, treatment, and prognosis 8. Hsa-miR-181a has been proposed to play a role in the pathogenesis, development, progression, metastasis, prognosis, and therapeutic response to chemo- and radiotherapy in EC,4,53 ovarian cancer,54 glioma,30,55 liver cancer,56 colorectal cancer,57–59 gastric cancer,60,61 lung cancer,62 breast cancer,63–67 cervical carcinoma,68,69 pancreatic cancer,46 osteosarcoma,70 oral squamous cell carcinoma,71,72 B-cell lymphoma,73 thyroid cancer,74 salivary adenoid cystic carcinoma,75 and acute and chronic leukemias 76–81. Ciafrè et al,82 firstly reported that the expression of hsa-miR-181a was significantly downregulated in primary glioblastomas and human glioblastoma cell lines compared with normal brain tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Hsa-miR-181a was upregulated in acute myeloid leukemia,76 especially in the M1 and M2 subtypes, and in myelodysplastic syndromes88 but downregulated in multiple myeloma89 and chronic lymphocyte leukemia 79,90. hsa-miR-181a can serve as an oncogene46,54,56–58,60,61,65,66,68–70,87,91 or tumor suppressor,55,67,71,75,78,79,92 implicating its multifaceted and complex roles in the regulation of its target genes and signaling pathways associated with cancer initiation, growth, development, progression, and metastasis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hsa-microRNA-181a is a regulator of a number of cancer genes and a biomarker for endometrial carcinoma in patients: a bioinformatic and clinical study and the therapeutic implication

Zeng

Zhou

et al. 2015

DDDT

View full text Add to dashboard Cite

The aberrant expression of human microRNA-181a-1 (hsa-miR-181a) has been implicated in the pathogenesis of various cancers, serving as an oncogene or a tumor suppressor. However, the role of hsa-miR-181a in the pathogenesis of endometrial carcinoma (EC) and its clinical significance are unclear. This study aimed to search for the molecular targets of hsa-miR-181a using bioinformatic tools and then determine the expression levels of hsa-miR-181a in normal, hyperplasia, and EC samples from humans. To predict the targets of hsa-miR-181a, ten different algorithms were used, including miRanda-mirSVR, DIANA microT v5.0, miRDB, RNA22 v2, TargetMiner, TargetScan 6.2, PicTar, MicroCosm Targets v5, and miRWALK. Two algorithms, TarBase 6.0 and miRTarBase, were used to identify the validated targets of hsa-miR-181a-5p (a mature product of hsa-miR-181a), and the web-based Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.7 was used to provide biological functional interpretation of the validated targets of hsa-miR-181a-5p. A total of 78 formalin-fixed, paraffin-embedded tissue specimens from 65 patients and 13 healthy subjects were collected and examined, including normal endometrium (n=13), endometrial hyperplasia (n=18), and EC (37 type I and 10 type II EC cases). Our bioinformatic studies have showed that hsa-miR-181a might regulate a large number of target genes that are important in the regulation of critical cell processes, such as cell fate, cell survival, metabolism, and cell death. To date, 313 targets of hsa-miR-181a have been validated, and 22 of these targets are cancer genes. The precision of predictions by all the algorithms for hsa-miR-181a-1’s targets was low. Many of these genes are involved in tumorigenesis of various cancers, including EC, based on the DAVID and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In comparison with normal endometrial tissue, the expression level of hsa-miR-181a was significantly increased in type I and type II EC (P<0.05), and type II EC exhibited a significant higher expression level of hsa-miR-181a than that in type I EC (P<0.05). In addition, there was a significant increase in the expression level of hsa-miR-181a in type II EC compared with endometrial hyperplasia (P<0.05). Taken together, these results suggest that hsa-miR-181a may serve as an oncogene in endometrial tumorigenesis and that hsa-miR-181a might be used as a new biomarker in the prediction of prognosis of EC in clinical practice. More functional and mechanistic studies are needed to validate the role of hsa-miR-181a in the development, progression, and metastasis of EC.

show abstract

miR‐181a mediates TGF‐β‐induced hepatocyte EMT and is dysregulated in cirrhosis and hepatocellular cancer

Abstract: MiR-181a had a direct effect in inducing hepatocyte EMT and was able to replace TGF-β-induced effects in vitro. MiR-181a was over-expressed in cirrhosis and HCC and is likely to play a role in disease pathogenesis.

Cited by 72 publications

References 38 publications

miR-744 is a potential prognostic marker in patients with hepatocellular carcinoma

miR-744 is a potential prognostic marker in patients with hepatocellular carcinoma

Impact of Tight Junction Protein ZO-1 and TWIST Expression on Postoperative Survival of Patients with Hepatocellular Carcinoma

Hsa-microRNA-181a is a regulator of a number of cancer genes and a biomarker for endometrial carcinoma in patients: a bioinformatic and clinical study and the therapeutic implication

Contact Info

Product

Resources

About