LncRNA H19 promotes triple-negative breast cancer cells invasion and metastasis through the p53/TNFAIP8 pathway

Abstract

Background: Long non-coding RNA H19 (lncRNA H19) has been implicated in tumorigenesis and metastasis of breast cancer through regulating epithelial to mesenchymal transition (EMT); however, the underlying mechanisms remain elusive. Methods: LncRNA H19 and TNFAIP8 were identified by qRT-PCR and western blotting. CCK-8 assay, clone formation assay, transwell assay, and flow cytometry assay were performed to determine cell proliferation, migration, invasion and cell cycle of breast cancer respectively. Western blotting and immunohistochemistry (IHC) were utilized to evaluate the protein expression levels of p53, TNFAIP8, and marker proteins of EMT cascades in vivo. Dual luciferase reporter assay and RNA pull down assay were conducted to evaluate the interactions of lncRNA H19, p53 and TNFAIP8. Results: The expression of lncRNA H19 and TNFAIP8 was up-regulated in breast cancer tissues and cell lines, especially in triple-negative breast cancer (TNBC). Functionally, knockdown of lncRNA H19 or TNFAIP8 coused the capacities of cell proliferation, migration, and invasion were suppressed, and cell cycle arrest was induced, as well as that the EMT markers were expressed abnormal. Mechanistically, lncRNA H19 antagonized p53 and increased expression of its target gene TNFAIP8 to promote EMT process. Furthermore, silencing of lncRNA H19 or TNFAIP8 also could inhibit tumorigenesis and lymph node metastases of MDA-MB-231 cells in xenograft nude mouse models. Conclusions: Our findings provide insight into a novel mechanism of lncRNA H19 in tumorigenesis and metastases of breast cancer and demonstrate H19/p53/TNFAIP8 axis as a promising therapeutic target for breast cancer, especially for TNBC.

Overexpression of Long Noncoding RNA H19 Downregulates miR-140-5p and Activates PI3K/AKT Signaling Pathway to Promote Invasion, Migration and Epithelial-Mesenchymal Transition of Ovarian Cancer Cells

“…LncRNA, as a highly active RNA, has been proved to participate in the genesis and development of a number of tumors [4]. Among them, lncRNA H19 has been found to be abnormally expressed in human malignant tumors and regulates cell proliferation, migration, invasion, antiapoptosis, and epithelial-mesenchymal transition (EMT) through various mechanisms, thus playing a carcinogenic or anticancer role [5][6][7]. H19 has been found to act as a microRNA sponge to indirectly regulate the expression of microRNA downstream target genes thus mediating cancer progression in several cancer types [8][9][10].…”

LncRNA SNHG6/miR-125b-5p/BMPR1B Axis: A New Therapeutic Target for Triple-Negative Breast Cancer

“…However, the exact effects of dysregulated lncRNA expressions have yet to be fully determined. Both breast cancer cell lines and samples, especially those of TNBC, have been found to harbor high expressions of lncRNA H19, which has been implicated to increased rates of metastasis and tumorigenesis (10). Moreover, lncRNA H19 may promote breast cancer tamoxifen resistance through modulation of the SAHH/DNMT3B axis (11).…”

The role and mechanism of long non-coding RNA H19 in stem cell osteogenic differentiation

“…H19, as a ceRNA, acted as a miR-140-5p sponge, resulting in regulated the expression of FGF9. Li et al found that H19 stimulates osteogenic differentiation of rat BMSCs via the H19/miR-149/SDF-1 axis (Li et al 2020a , b ). Overexpressed H19 and SDF-1 and poorly expressed miR-149 were found in rats with osteogenic differentiation.…”

“…In recent years, mounting evidence has shown that various new bioinformatical and experimental strategies have identified a large number of novel lncRNAs (Lee and Bartolomei 2013 ; Batista and Chang, 2013 ; Alipoor et al 2020 ). LncRNAs could regulate gene expressions through interactions with DNAs, RNAs, protein (Koch 2017 ; Ali and Grote 2020; Cardon et al 2020 ; Li et al 2020a , b ; Zhang et al 2021 ), including chromatin remodeling, as well as transcriptional, post-transcriptional and epigenetic regulations (Lee and Bartolomei, 2013 ; Fatica and Bozzoni, 2014 ; Graf and Kretz 2020 ; Li et al 2020a , b ).…”

“…As one of the most well-known lncRNAs, H19 has been implicated in human disorders through various molecular mechanisms, including controlling of RNA progressing, cellular proliferation, differentiation, and disease development (Ratajczak 2012 ). The diagnostic and therapeutic importance of H19 in human cancer has been widely established (Alipoor et al 2020 ; Shermane et al 2021 ) , such as breast cancer (Li et al 2020a , b ), lung cancer (Xu et al 2019 ) . H19 was also shown to play an important role in various cardiovascular diseases such as acute myocardial infarction (Huang et al 2020 ), myocardial I/RI (Li et al 2019a , b ) and cardiomyocyte hypertrophy (Viereck et al 2020 ).…”