Dual targeting of ANGPT1 and TGFBR2 genes by miR-204 controls angiogenesis in breast cancer

Chen

et al. 2017

Cell Physiol Biochem

Background/Aims: Increasing evidence indicates that Huaier extract has promising therapeutic effects against cancer. However, the mechanisms that underlie its anti-tumor effects remain unclear. In recent years, various studies have shown that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cancer development and progression. Here, we explored the role of lncRNAs in Huaier-induced tumor suppression. Methods: Microarray profiling was performed to identify the candidate lncRNAs affected by Huaier extract. Quantitative realtime PCR (qPCR) was used to evaluate the transfection efficiency and the influence of Huaier extract on H19 expression. The effect of Huaier extract on the cell viability was examined by MTT. Moreover, the rates of apoptotic cells were detected using flow-cytometric analysis. Western blot analysis was applied to show the protein levels of CBL. Results: Microarray data derived from Huaier-treated breast cancer cells identified H19 as a potential target. Huaier extract reduced the expression of H19. The over-expression of H19 inhibited the cytotoxic effects of Huaier extract; in contrast, reduced H19 expression enhanced the function of Huaier extract. MiR-675-5p was identified as a mature product of H19. Moreover, Huaier extract reduced the miR-675-5p expression. Upregulating miR-675-5p reversed the inhibitory effects of Huaier extract, whereas downregulating miR-675-5p sensitized breast cancer cells to the effect of Huaier extract. In addition, Huaier extract increased the expression of CBL protein, a direct target of miR-675-5p. Conclusion: Collectively, the data demonstrate that Huaier extract reduces viability and induces apoptosis in breast cancer cells via H19-miR-675-5p-CBL axis regulation.

Section: Discussionmentioning

confidence: 99%

Huaier Extract Inhibits Breast Cancer Progression Through a LncRNA-H19/MiR-675-5p Pathway

Chen

et al. 2017

Cell Physiol Biochem

“…Recently, several reports have proved that miR‐204 generally acts as a tumor suppressor in human cancer (Shi et al, ). Its expression is significantly downregulated in several cancers including gastric cancer, colorectal cancer, breast cancer, and hepatocellular carcinoma, as it inhibits cellular proliferation, migration, and invasion (Flores‐Pérez et al, ; Jiang, Wen, Zheng, Jian, & Deng, ; Sacconi et al, ; Yin et al, ). However, there have been very few reports about the role of miR‐204 on the adipocyte development.…”

Section: Introductionmentioning

confidence: 99%

Role of bta‐miR‐204 in the regulation of adipocyte proliferation, differentiation, and apoptosis

Jin

Journal Cellular Physiology

Zhang

et al. 2019

Adipocyte growth and development are complex and precisely orchestrated processes. Several microRNAs have been identified as critical regulators of the adipocyte growth and development. Recently, bta‐miR‐204 was found to be involved in adipogenesis; however, the underlying molecular mechanism involved in bta‐miR‐204‐mediated regulation of proliferation, differentiation, and apoptosis of adipocytes is not fully understood or elucidated. In this study, quantitative real‐time polymerase chain reaction (qRT‐PCR), Cell Counting Kit‐8, EdU, flow cytometer, Oil Red O staining, and the western blot assays were used to assess the role of bta‐miR‐204 in adipocyte growth and development. Overexpression of bta‐miR‐204 had no significant effect on 3T3‐L1 cell proliferation. The forced expression of bta‐miR‐204 promoted 3T3‐L1 cell differentiation. Meanwhile, overexpression of bta‐miR‐204 upregulated the expression of Bax and downregulated the expression of Bcl‐2 both at messenger RNA and protein levels, which suggested that bta‐miR‐204 can promote 3T3‐L1 cell apoptosis. Using bioinformatic analysis, dual‐luciferase reporter system and qRT‐PCR, TGFBR2, and ELOVL6 were identified as the direct target genes of bta‐miR‐204. Therefore, our study provides a novel insight into the role of bta‐miR‐204 in the regulation of adipocyte growth and development, which may provide a novel therapeutic alternative against obesity.

“…Adipose tissue dysfunction directly and indirectly leads to dyslipidemia, hyperglycemia, and hypertension due to excessive caloric imbalance. Flores-Perez et al 26 found that miR-204 regulates tumor angiogenesis by targeting ANGPT1 and TGFBR2 in breast cancer. 23 Therefore, an in-depth understanding of fat deposition in pig adipose tissue can contribute to biomedical research.…”

Section: Discussionmentioning

confidence: 99%

ssc‐miR‐204 regulates porcine preadipocyte differentiation and apoptosis by targeting TGFBR1 and TGFBR2

Zhang

J of Cellular Biochemistry

et al. 2019

MicroRNAs (miRNAs) take part in a variety of biological processes by regulating target genes. Transforming growth factor β receptor 1 (TGFBR1) and TGFBR2 are crucial members of the TGF‐β family and are serine/threonine kinase receptors. The aim of this study was to explore the functions of ssc‐miR‐204 in porcine preadipocyte differentiation and apoptosis with regard to the TGFβ/Smad pathway. We identified miRNAs predicted to target TGFBR1 and TGFBR2 using a database and selected ssc‐miR‐204 as a candidate miRNA. ssc‐miR‐204 overexpression dramatically reduced the levels of TGFBR1 and TGFBR2. However, after transfection with ssc‐miR‐204 inhibitor, TGFBR1 and TGFBR2 levels were dramatically increased. ssc‐miR‐204 overexpression dramatically promoted porcine preadipocyte differentiation and apoptosis. After transfection with ssc‐miR‐204 inhibitor, porcine preadipocyte differentiation and apoptosis were dramatically inhibited. After transfection with ssc‐miR‐204 mimics, Smad2, Smad3, Smad4, p‐Smad2, and p‐Smad3 protein levels significantly decreased, and adipogenesis was regulated by inhibiting the TGF‐β/Smad3 signaling pathway. Taken together, these results verified that ssc‐miR‐204 regulates porcine preadipocyte differentiation and apoptosis by targeting TGFBR1 and TGFBR2.