MiR-516a-3p is a Novel Mediator of Hepatocellular Carcinoma Oncogenic Activity and Cellular Metabolism

Tao, Rui; Zhang, Xueyou; Feng, Shi Ting; Huang, Haitao; Zhan, Shaowei; Xie, Haiyang; Zhou, Lin; Zheng, Shusen; Ling, Qi

doi:10.1016/j.eng.2021.07.020

Cited by 6 publications

(4 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We identified exosome after the exosome purification. Transmission electron microscopy (TEM) was performed as previously described, 18 the purified exosomes were seeded on a copper grid and negatively stained with phosphotungstic acid (2%) for 1.5 min. After the samples were dried for 15 min, the exosomes were observed with a transmission electron microscope (Tecnai G2 Spirit 120 kV, Thermo Fisher Scientific, St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Serum Exosome-Derived piRNAs Could Be Promising Biomarkers for HCC Diagnosis

Tao¹,

Wang²,

Xiang³

et al. 2023

IJN

Self Cite

View full text Add to dashboard Cite

Background Serum exosome-based liquid biopsy has significant advantages for screening and diagnosing hepatocellular carcinoma (HCC). P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel small silencing RNAs that have been identified to function in cancer-related signalling pathways. However, studies on the presence of piRNAs in serum exosomes from HCC patients and their diagnostic values in HCC are not well reported. Our aim is to validate serum exosome-derived piRNAs as the valuable component of liquid biopsy for diagnosing HCC. Methods We used small RNA (sRNA) sequencing to profile piRNAs from serum exosomes and describe the base distribution characteristics of serum exosome-derived piRNAs. Serum exosomes from 125 HCC patients and 44 nontumor donors were included in this study. Results We found that piRNAs were components of serum exosomes from HCC patients. A total of 253 differentially expressed serum exosome-derived piRNAs were screened from HCC compared with the piRNAs from nontumor donors. Serum exosome-derived piRNAs from HCC displayed a distinctive base distribution. To further confirm the potential diagnostic value of serum exosome-derived piRNAs in HCC, we detected the levels of the top 5 upregulated piRNAs in our Chinese cohort. The training set and validation set both showed that all 5 piRNAs were dramatically increased in the serum exosomes from HCC compared with the piRNAs from non-tumour donors. The piRNAs could strongly identify HCC patients from non-tumour donors according to the area under the receiver operating characteristic (AUROC) model. Additionally, the piRNAs could also present significant values for the diagnosis of HCC with low tumour burden. Conclusion piRNAs enriched the components of serum exosomes from HCC and could serve as promising biomarkers for HCC diagnosis.

show abstract

Section: Methodsmentioning

confidence: 99%

“…As previously described, 18 the protein from the purified exosomes was extracted and electrophoresed on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel (FD341-100, Fudebio, Hangzhou, China). Then, all the proteins were transferred onto equilibrated polyvinylidene difluoride membranes.…”

Section: Methodsmentioning

confidence: 99%

Serum Exosome-Derived piRNAs Could Be Promising Biomarkers for HCC Diagnosis

Tao¹,

Wang²,

Xiang³

et al. 2023

IJN

Self Cite

View full text Add to dashboard Cite

show abstract

“…The sequences of the wild-type or mutant-type 3′ untranslated region sites of DBF4 or XPO1 were respectively synthesized and constructed into pmirGLO vector (Repobio, China), as previously described. 23 , 24 Cells were transfected with the corresponding reporter plasmids using Lipofectamine 2000 (Invitrogen, USA). The pRL-TK reporter construct was used for internal control.…”

Section: Methodsmentioning

confidence: 99%

DBF4 Dependent Kinase Inhibition Suppresses Hepatocellular Carcinoma Progression and Potentiates Anti-Programmed Cell Death-1 Therapy

Zhang¹,

Hong²,

Cui³

et al. 2023

Int. J. Biol. Sci.

Self Cite

View full text Add to dashboard Cite

The progression of hepatocellular carcinoma (HCC) remains a huge clinical challenge, and elucidation of the underlying molecular mechanisms is critical to develop effective therapeutic strategy. Dumbbell former 4 (DBF4) complexes with cell division cycle 7 (CDC7) to form DBF4-dependent kinase (DDK), playing instrumental roles in tumor cell survival, whereas its roles in HCC remain elusive. This study revealed that DBF4 expression was upregulated in HCC and constituted an independent prognostic factor of patient survival. We identified p65 as an upstream inducer which increased DBF4 expression by directly binding to its promoter. DBF4 accelerated HCC cell proliferation and tumorigenesis in vitro and in vivo . Mechanistically, DBF4 complexed with CDC7 to bind to the coiled coil domain of STAT3 and activate STAT3 signaling through XPO1-mediated nuclear exportation. Notably, p65 enhanced the nuclear transport of DDK and DDK-STAT3 interaction by transcriptionally upregulating XPO1. DBF4 expression positively correlated with activated STAT3 and XPO1 in HCC tissues. Furthermore, combining DDK inhibitor XL413 with anti-PD-1 immunotherapy dramatically suppressed HCC growth and prolonged the survival of HCC-bearing mouse. Our findings reveal that DDK activates STAT3 pathway and facilitates HCC progression, and demonstrate the proof of the concept of targeting DDK to improve the efficacy of HCC immunotherapy.

show abstract

“…As described previously ( Rui et al, 2021 ), the pmirGLO vector (Repobio, China) was designed to assess the inhibitory effect of miRNAs by measuring the luciferase activity. The sequences of wild-type or the mutant-type 3’ untranslated regions (3’UTRs) of the ESR were cloned into the pmirGLO vector.…”

Section: Methodsmentioning

confidence: 99%

Mir-4728 is a Valuable Biomarker for Diagnostic and Prognostic Assessment of HER2-Positive Breast Cancer

Tao

Xiang

Guo

et al. 2022

Front. Mol. Biosci.

Self Cite

View full text Add to dashboard Cite

Breast cancer remains one of the most common malignancies in female cancer patients. The rapid and accurate diagnosis of human epidermal growth factor receptor 2 (HER2) status is indispensable for breast cancer patients. The pre-miR-4728 (mir-4728) is encoded within an intron of the HER2 gene. We showed here that mir-4728 was the most significantly upregulated pre-miRNA in HER2-positive breast cancer patients (fold-change: 4.37), and it could serve as a strong diagnostic factor for the HER2 status in breast cancer patients (p < 0.0001). Moreover, mir-4728 was positively correlated with tumor recurrence and appeared to be a critical independent risk factor of tumor recurrence in patients with high tumor burden (HR: 7.558, 95% CI:1.842-31.006, p = 0.005). Remarkably, HER2-positive patients with higher mir-4728 expression levels had better drug responses to targeted therapies. Furthermore, estrogen receptor (ESR), the predictive marker for endocrine therapies, was found to be the direct target of miR-4728-3p. Taken together, our results supported the potential role of mir-4728 in the diagnosis of HER2 status and the prognostic assessment of HER2-positive patients in response to targeted therapies.

show abstract

MiR-516a-3p is a Novel Mediator of Hepatocellular Carcinoma Oncogenic Activity and Cellular Metabolism

Cited by 6 publications

References 44 publications

Serum Exosome-Derived piRNAs Could Be Promising Biomarkers for HCC Diagnosis

Serum Exosome-Derived piRNAs Could Be Promising Biomarkers for HCC Diagnosis

DBF4 Dependent Kinase Inhibition Suppresses Hepatocellular Carcinoma Progression and Potentiates Anti-Programmed Cell Death-1 Therapy

Mir-4728 is a Valuable Biomarker for Diagnostic and Prognostic Assessment of HER2-Positive Breast Cancer

Contact Info

Product

Resources

About