MicroRNA-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma

Zhao

Oxidative Medicine and Cellular Longevity

et al. 2022

Background. DCM is the most common and malignant complication of diabetes. It is characterized by myocardial dilatation, hypertrophy, fibrosis, ventricular remodeling, and contractile dysfunction. Although many studies have demonstrated the function of miRNAs in the progression of DCM, but the specific role of miR-372-3p in DCM remains unknown. Methods. C57/BL6J mice were used to construct mouse models of DCM by intraperitoneal injection of STZ (50 mg/kg/d) for 5 consecutive days. Then the mice were randomly divided into model group (intramyocardial injection of empty lentivirus) and miR-372-3p KD group (intramyocardial injection of miR-372-3p KD lentivirus at 10 9 /mouse). Besides, the control group (injection of 0.9% normal saline) was also set up. LY294002, a PI3K inhibitor, was employed in the current study. Western blotting, immunofluorescence staining, quantitative ultrasound method, Masson's trichrome staining, and bioinformatics analysis were performed. Results. It was found that miR-372-3p KD significantly improved left ventricular dysfunction and cardiac hypertrophy in DCM mice. Furthermore, it also improved myocardial interstitial fibrosis and remodeling in DCM mice. Immunofluorescence staining and RT-qPCR revealed that miR-372-3p KD might accelerate cardiac remodeling by increasing angiogenesis in DCM mice. Western blotting results revealed that miR-372-3p was an upstream target of the PI3K/ AKT-mTOR and HIF-1α signals, as well as NOX2, NOX4, which were responsible for angiogenesis in DCM mice. Besides, the in vitro experiment showed that LY294002 markedly diminished the increased expression levels of p-PI3K, AKT, p-mTOR, p-P70S6K, HIF-1α, NOX2, and NOX4 in the model group and the miR-372-3p KD group, suggesting that PI3K signaling pathway and oxidative stress are involved in miR-372-3p KD-induced angiogenesis in HG-stimulated C166 cells. Conclusions. MiR-372-3p KD inhibits the development of DCM via activating the PI3K/AKT/mTOR/HIF-1α signaling pathway or suppressing oxidative stress. This offers an applicable biomarker for DCM treatment.

Section: Introductionmentioning

confidence: 99%

Knockdown of miR-372-3p Inhibits the Development of Diabetic Cardiomyopathy by Accelerating Angiogenesis via Activating the PI3K/AKT/mTOR/HIF-1α Signaling Pathway and Suppressing Oxidative Stress

Zhao

Oxidative Medicine and Cellular Longevity

et al. 2022

“…Co-transfection of miR-372-3p (mimics/inhibitors) and twist1 (mimics/inhibitors) demonstrated that twist1 could partially reverse the effects of miR-372-3p (mimics/inhibitors) on trophoblast cells, which suggested that miR-372-3p may suppress trophoblast migration, invasion and EMT (E-cadherin, N-cadherin, vimentin and twist1) by targeting twist1. Previous studies have reported that miR-372-3p serves important roles in numerous types of disease, for example colorectal cancer, lung squamous cell carcinoma, osteosarcoma, hepatocellular carcinoma (8,(32)(33)(34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

miR‑372‑3p promotes preeclampsia progression by regulating twist1

Wang

Chen

et al. 2022

Exp Ther Med

Preeclampsia (PE) is a common pregnancy-related disorder worldwide. PE is mainly characterized by the defective migration and invasion of trophoblast cells. MicroRNAs (miRs) have been reported to serve an important role in PE. The purpose of the study was to explore the pathogenesis and therapeutic targets of preeclampsia. In the present study, reverse transcription-quantitative PCR analysis revealed that the expression levels of miR-372-3p were upregulated in placental tissues from patients with PE. Notably, the expression levels of miR-372-3p were significantly upregulated in patients with early-onset PE compared with patients with late-onset PE. Moreover, in vitro analysis using wound healing, Transwell and western blotting assays demonstrated that miR-372-3p overexpression inhibited the migration, invasion and epithelial-mesenchymal transition (EMT) of HTR-8/ SVneo trophoblast cells, respectively. Bioinformatics analysis and a dual luciferase reporter assay revealed that miR-372-3p is sponged by twist family bHLH transcription factor 1 (twist1). Rescue experiments found that miR-372-3p overexpression suppressed trophoblast cell migration, invasion and EMT by downregulating the expression of twist1. In conclusion, the present study revealed that high level of miR-372-3p may act as a factor to cause PE and may also be a potential novel therapeutic target for PE.

“…In addition to the relatively novel lncRNAs, microRNAs (miRNAs) remain a focus of research on nucleic acid biomarkers [ 74 ]. miRNA-372-3p, which acts as a tumor suppressor in HCC, has been demonstrated to play a crucial role in cellular proliferation, apoptosis, and metastasis of various cancers, including HCC, colon cancer, and osteosarcoma [ 75 , 76 , 77 ]. Consistent with this, ectopic expression of miR-372-3p reduces cell proliferation and migration and significantly induces apoptosis in HepG2 cells in association with a decrease in the antiapoptotic protein Mcl-1 [ 75 ].…”

Section: Genes Associated With Doxorubicin Resistancementioning

confidence: 99%

“…miRNA-372-3p, which acts as a tumor suppressor in HCC, has been demonstrated to play a crucial role in cellular proliferation, apoptosis, and metastasis of various cancers, including HCC, colon cancer, and osteosarcoma [ 75 , 76 , 77 ]. Consistent with this, ectopic expression of miR-372-3p reduces cell proliferation and migration and significantly induces apoptosis in HepG2 cells in association with a decrease in the antiapoptotic protein Mcl-1 [ 75 ]. Notably, levels of miR-372-3p in the blood of HCC patients responsive to TACE with doxorubicin are significantly higher than those in nonresponders.…”

Section: Genes Associated With Doxorubicin Resistancementioning

confidence: 99%

Evaluation and Application of Drug Resistance by Biomarkers in the Clinical Treatment of Liver Cancer

Huang

Wang

et al. 2023

Cells

Liver cancer is one of the most lethal cancers in the world, mainly owing to the lack of effective means for early monitoring and treatment. Accordingly, there is considerable research interest in various clinically applicable methods for addressing these unmet needs. At present, the most commonly used biomarker for the early diagnosis of liver cancer is alpha-fetoprotein (AFP), but AFP is sensitive to interference from other factors and cannot really be used as the basis for determining liver cancer. Treatment options in addition to liver surgery (resection, transplantation) include radiation therapy, chemotherapy, and targeted therapy. However, even more expensive targeted drug therapies have a limited impact on the clinical outcome of liver cancer. One of the big reasons is the rapid emergence of drug resistance. Therefore, in addition to finding effective biomarkers for early diagnosis, an important focus of current discussions is on how to effectively adjust and select drug strategies and guidelines for the treatment of liver cancer patients. In this review, we bring this thought process to the drug resistance problem faced by different treatment strategies, approaching it from the perspective of gene expression and molecular biology and the possibility of finding effective solutions.