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

Abstract

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.

The Dysregulated Expression of KCNQ1OT1 and Its Interaction with Downstream Factors miR-145/CCNE2 in Breast Cancer Cells

“…LncRNAs have been found to function as competing endogenous RNAs where they sponge miRNAs and regulate miRNA targets [16]. Wang et al found that Huaier extract inhibited BRCA through lncRNA-H19/miR-675-5p [17]. In the present study, the dysregulated expression of the lncRNA KCNQ1OT1 was found to be significantly associated with BRCA progression.…”

Long noncoding MAGI2‐AS3 promotes colorectal cancer progression through regulating miR‐3163/TMEM106B axis

“…Considerable studies verified that lncRNAs exert their effects on diverse cancers, such as lung cancer, esophageal squamous cell carcinoma, and breast cancer (Seiler et al, 2017;Wang, Wang, Chen, Jiang, & Yang, 2017;Wu et al, 2017). As a new found lncRNA, MAGI2-AS3 has not been extensively reported in cancers.…”

Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis

“…In tumors, abnormal expression of lncRNAs contributes to the development and progression of cancer by influencing proliferation, apoptosis, autophagy, metastasis, self-renewal, and survival via epigenetic, transcriptional, and post-transcriptional gene regulatory mechanisms [10][11][12]. Furthermore, aberrant expression of lncRNAs can be detected in circulating cancer cells and in the serum and urine of cancer patients, which suggests that lncRNAs may serve as an effective biomarker for cancer detection and prognosis [13,14].…”