Exosomal lncRNA ATB Derived from Ovarian Cancer Cells Promotes Angiogenesis via Regulating miR-204-3p/TGFβR2 Axis

Abstract

Background Ovarian cancer is a life-threatening disease with a high mortality rate in women. Our previous work presented that long non-coding RNA (lncRNA) activated by transforming growth factor beta (TGF-β) (lncRNA ATB) played a role of oncogene in ovarian cancer. However, whether exosomal lncRNA ATB from ovarian cancer cells could regulate the tumorigenesis of ovarian cancer remains unclear. Methods RT-qPCR assay was performed to evaluate the level of lncRNA ATB in cancer cells (SKOV3 and A2780). In addition, ovarian cancer cells-secreted exosomes were collected with ultracentrifugation. CCK8 assay was performed to detect the viability of ovarian cells and HUVECs. Meanwhile, Western blot was performed to detect the expression of mechanism related protein and tube formation assay was used to observe the angiogenesis of HUVECs. Finally, xenograft mice model was used to verify the role of ovarian cancer cell-derived exosomes in vivo. Results Ovarian cancer cells-derived exosomes promoted the viability, angiogenesis and migration of HUVECs; however, knockdown of lncRNA ATB in HUVECs reversed these phenomena. In addition, exosomal lncRNA ATB promoted the tumorigenesis of ovarian cancer via regulating miR-204-3p/TGFβR2 axis. Furthermore, ovarian cancer cells-secreted exosomal lncRNA ATB increased tumor growth in vivo. Conclusion Exosomal lncRNA ATB derived from ovarian cancer cells could improve tumor microenvironment via regulating miR-204-3p/TGFβR2 axis. Thus, this study might provide new knowledge for the treatment of ovarian cancer.

Extracellular Vesicles as Delivery Shippers for Noncoding RNA‐Based Modulation of Angiogenesis: Insights from Ischemic Stroke and Cancer

“…[174,181,197] Among these lncRNAs, NORAD, OIP5-AS1, ARSR, SNHG1, and ATB were upregulated in skeletal, urinary, and reproductive system tissues and facilitated cancer development. [175,224,226,239,225] In contrast, the remaining nine lncRNAs (GAS5, LINC01915, LINC00662, FAM225A, SNHG16, LINC00161, SNHG11, CCAT1, and UCA1), GAS5 with LINC01915 were downregulated in respiratory and colorectal cancer, [180,213] the left were upregulated in digestive cancer tissues and promoted oesophageal adenocarcinoma, hepatocellular and pancreatic cancer progression. [187,190,196,201,236,237,248] It is well documented that EVs and miRNAs are irreplaceable intercellular communication tools and have received great attention due to their modulation of angiogenesis.…”

“…Seventy‐six publications were found in this section, from Iran, Japan, China, Korea, and India, performed between 2013 and 2022. [ 127,174–248 ] Of these ncRNAs, 3 circRNAs, 14 lncRNAs, and 45 microRNAs were differentially expressed between healthy individuals and various cancers. Concerning circRNAs (namely, circHIPK3, circFNDC3B, and circCMTM3 derived from EVs) are upregulated and shown to regulate metatherian, tissue inhibitor of metalloproteinase 3, SOX9 through miR‐124‐3p, miR‐937‐5p, miR‐3619‐5p in breast cancer, colorectal cancer, and hepatocellular carcinoma, respectively, which enhance EC viability, migration and tube formation except in colorectal cancer to drive the process of carcinogenesis.…”

Regulation of temozolomide resistance via lncRNAs: Clinical and biological properties of lncRNAs in gliomas (Review)

“…In 2012, Zhang et al (33) first associated lncRNA expression with the grade of malignancy in human glioma. Furthermore, lncRNAs have been reported to be associated with the occurrence and progression of various malignancies such as colorectal cancer, gallbladder cancer, ovarian cancer in addition to modulating chemoresistance in glioma (34)(35)(36)(37)(38). The expression of a number of lncRNAs has been found to be upregulated in glioma and these lncRNAs have been proposed to function as oncogenes, whilst the expression levels of other lncRNAs have been found to be downregulated in glioma and those lncRNAs have been proposed to function as tumor suppressor genes.…”

Advances in Exosomes as Diagnostic and Therapeutic Biomarkers for Gynaecological Malignancies

“…Ovarian cancer cell-derived exosomes encourage the angiogenesis and migration of vascular endothelial cells in vitro and in vivo, which includes exosomal miR-130a [36], lncRNA ATB [37], and PKR1 [38] playing a role in it, while miR-92b-3p [39] secreted by OC cells is antiangiogenic in OC.…”