Hepatitis B virus X protein mutant HBxΔ127 promotes proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT

Liu, Fabao; You, Xiaona; Chi, Xiumei; Wang, Tao; Ye, Lihong; Niu, Junqi; Zhang, Xiaodong

doi:10.1016/j.bbrc.2014.01.004

Cited by 32 publications

(25 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although over-expression of miR-215 impedes the progression of colon and renal cancer (Jones et al, 2015; Senanayake et al, 2012), miR-215 is shown to serve as an onco-mir in the development of gastric cancer and hepatoma (Deng et al, 2014; Liu et al, 2014). Since miR-215 is induced in GICs under hypoxia and attenuation of its function significantly delayed tumor progression (Figure 1A), we further examined the role of miR-215 in GICs.…”

Section: Resultsmentioning

confidence: 99%

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B

Sun

Wang

et al. 2016

Cancer Cell

View full text Add to dashboard Cite

SUMMARY The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit the hypoxic microenvironment via suppressing the expression of an epigenetic regulator KDM1B and modulating activities of multiple pathways. Interestingly, biogenesis of miR-215 and several miRNAs is accelerated post-transcriptionally by hypoxia-inducible factors (HIFs) through HIF-Drosha interaction. Moreover, miR-215 expression correlates inversely with KDM1B while positively with HIF1α and GBM progression in patients. These findings reveal a direct role of HIF in regulating miRNA biogenesis and consequently activating the miR-215-KDM1B-mediated signaling required for GIC adaptation to hypoxia.

show abstract

Section: Resultsmentioning

confidence: 99%

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B

Sun

Wang

et al. 2016

Cancer Cell

View full text Add to dashboard Cite

show abstract

“…Researchers previously identified a natural mutant of the HBx gene with C-terminal-deletion from 382 to 401 bp (termed HBxΔ127), which strongly enhanced cell proliferation and migration in HCC relative to wild-type HBx (69). The specific mechanism is that HBxΔ127 strongly upregulates miR-215 in hepatoma cells, and the latter directly targets PTPRT (protein tyrosine phosphatase, receptor type T) mRNA which normally acts as a tumor suppressor (49). Another important C-terminaldeletion formation is HBxΔ35.…”

Section: The Effect Of the Particular Hbx Form On Mirnamentioning

confidence: 99%

“…For regulating miR-21, HBx and HBxΔ35 play a part concurrently. Discriminatively, HBx protein increases the expression of miR-21 directly, on the contrary, HBxΔ35 depends on IL-6 and STAT3 which are the targets of HBxΔ127 at the same time, and HBxΔ127 regulates the STAT3 through inducing the miR-215 and repressing protein tyrosine phosphatase receptor type T (PTPRT) which is a tumor suppressor (37,48,49).…”

Section: The Influence Of Hbx Through Regulating Mirna For Hepatocarcmentioning

confidence: 99%

The function of miRNAs in hepatocarcinogenesis induced by hepatitis B virus X protein

Wang

Huang

2017

Oncology Reports

View full text Add to dashboard Cite

MicroRNAs are short RNAs that play a crucial role in all biological processes through post-transcriptional regulation for protein-coding genes and inducing mRNA degradation. Hepatitis B virus infection has been considered as a major risk factor in hepatocellular carcinoma, further research indicates that hepatitis B virus X protein (HBx) is one of the critical links of hepatocarcinogenesis. HBx takes part in hepatocarcinogenesis via regulating transcription, signal transduction, apoptosis, protein degradation and DNA repair. miRNA is the important target gene of HBx, their interaction impacts many tumor processes, such as proliferation, apoptosis, invasion, metastasis, differentiation and adipogenesis. In the present study we reviewed the current state of knowledge of regulation pathway of HBx acting on miRNAs, and focused on the role of their interplay in hepatocarcinogenesis.

show abstract

“…In addition to genetic mutations of the PTPRT coding sequence, alterations in promoter methylation status of the PTPRT gene have been noted in colorectal cancer [68]. microRNAs targeting PTPρ mRNA have been observed following hepatitis virus B infection [69] and in side population cells (that are similar to cancer stem cells) from the MCF7 breast cancer cell line [70]. These microRNAs disrupt PTPρ function in cancer cells by reducing the amount of wild-type PTPρ protein.…”

Section: Alteration Of R2b Rptps In Cancermentioning

confidence: 99%

Regulation of development and cancer by the R2B subfamily of RPTPs and the implications of proteolysis

Craig

Brady‐Kalnay

2015

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

The initial cloning of receptor protein tyrosine phosphatases (RPTPs) was met with excitement because of their hypothesized function in counterbalancing receptor tyrosine kinase signaling. In recent years, members of a subfamily of RPTPs with homophilic cell-cell adhesion capabilities, known as the R2B subfamily, have been shown to have functions beyond that of counteracting tyrosine kinase activity, by independently influencing cell signaling in their own right and by regulating cell adhesion. The R2B subfamily is composed of four members: PTPmu (PTPRM), PTPrho (PTPRT), PTPkappa (PTPRK), and PCP-2 (PTPRU). The effects of this small subfamily of RPTPs is far reaching, influencing several developmental processes and cancer. In fact, R2B RPTPs are predicted to be tumor suppressors and are among the most frequently mutated protein tyrosine phosphatases (PTPs) in cancer. Confounding these conclusions are more recent studies suggesting that proteolysis of the full-length R2B RPTPs result in oncogenic extracellular and intracellular protein fragments. This review discusses the current knowledge of the role of R2B RPTPs in development and cancer, with special detail given to the mechanisms and implications that proteolysis has on R2B RPTP function. We also touch upon the concept of exploiting R2B proteolysis to develop cancer imaging tools, and consider the effects of R2B proteolysis on axon guidance, perineural invasion and collective cell migration.

show abstract

Hepatitis B virus X protein mutant HBxΔ127 promotes proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT

Cited by 32 publications

References 37 publications

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B

The function of miRNAs in hepatocarcinogenesis induced by hepatitis B virus X protein

Regulation of development and cancer by the R2B subfamily of RPTPs and the implications of proteolysis

Contact Info

Product

Resources

About