CircTHBS1 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-136-3p/IGF2R axis.

The precise molecular mechanism behind fetal growth restriction (FGR) is still unclear, although there is a strong connection between placental dysfunction, inadequate trophoblast invasion, and its etiology and pathogenesis. As a new type of non-coding RNA, circRNA has been shown to play a crucial role in the development of FGR. This investigation identified the downregulation of hsa_circ_0034533 (circTHBS1) in FGR placentas through high-sequencing analysis and confirmed this finding in 25 clinical placenta samples using qRT-PCR. Subsequent in vitro functional assays demonstrated that silencing circTHBS1 inhibited trophoblast proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression and promoted apoptosis. Furthermore, when circTHBS1 was overexpressed, cell function experiments showed the opposite result. Analysis using fluorescence in situ hybridization revealed that circTHBS1 was primarily found in the cytoplasmic region. Through bioinformatics analysis, we anticipated the involvement of miR-136-3p and IGF2R in downstream processes, which was subsequently validated through qRT-PCR and dual-luciferase assays. Moreover, the inhibition of miR-136-3p or the overexpression of IGF2R partially reinstated proliferation, migration, and invasion abilities following the silencing of circTHBS1. In summary, the circTHBS1/miR-136-3p/IGF2R axis plays a crucial role in the progression and development of FGR, offering potential avenues for the exploration of biological indicators and treatment targets.

CircTHBS1 facilitates the progression of interstitial cystitis depending on the regulation of miR-139-5p/MFN2 axis.

Circular RNA (circRNA) have been found to play an important role in the progression of many diseases, including interstitial cystitis (IC). However, the role of circTHBS1 in IC progression is still unclear. Exploring the role and potential molecular mechanism of circTHBS1 in the development of IC. The enzyme-linked immunosorbent assay was used to assess the levels of inflammatory cytokines. The expression levels of circTHBS1, microRNA (miR)-139-5p, and mitofusin 2 (MFN2) were evaluated using quantitative real-time PCR. Cell proliferation and migration were determined using MTT assay, Edu staining, and transwell assay. The protein levels of epithelial-mesenchymal transition (EMT) markers and MFN2 were examined using western blot analysis. The relationship between miR-139-5p and circTHBS1 or MFN2 was confirmed using the dual-luciferase reporter assay and RIP assay. CircTHBS1 was highly repressed in IC tissues and cells, and its expression was positively correlated with the inflammatory response of IC patients. CircTHBS1 could promote the proliferation, migration, EMT process, and inflammation of IC cells, while its knockdown had an opposite effect. CircTHBS1 could serve as a sponge of miR-139-5p, and miR-139-5p could participate in the regulation of circTHBS1 on IC cell progression. In addition, miR-139-5p could target MFN2, and it could inhibit the progression of IC cells by targeting MFN2. Furthermore, circTHBS1 sponged miR-139-5p to positively regulate MFN2. CircTHBS1 promoted IC cell proliferation, migration, EMT process, and inflammation by regulating the miR-139-5p/MFN2 axis indicating that circTHBS1 might be a potential target for IC treatment.

CircTHBS1 targeting miR-211/CCND2 pathway to promote cell proliferation and migration potential in primary cystitis glandularis cells.

The pathogenesis of cystitis glandular (CG) is unclear, but it is generally considered to be a neoplastic lesion of urothelial hyperplasia formed by long-term chronic stimulation. There is growing evidence that circRNAs play important roles in a variety of cellular processes. However, there are few reports on the role and molecular mechanism of circRNA in CG. In the present study, we first isolated primary cells from CG tissues and adjacent normal tissues. Further experiments showed that CircTHBS1 was up-regulated in primary CG cells (pCGs). The results of CCK-8 showed that the overexpression of CircTHBS1 promoted the viability of pCGs, while the deletion of CircTHBS1 reduced the cell viability. Knocking out CircTHBS1 also inhibited the migration of pCGs. In addition, we demonstrated that CircTHBS1 played a role in the adsorption of miR-211 by "sponge" in pCG. In turn, miR-211 can directly target CYCLIN D2 (CCND2) 3'UTR to perform its function. Finally, we confirmed the role and mechanism of CircTHBS1/miR-211/CCND2 regulation axis in pCGs. In summary, our study is the first to reveal the role and underlying mechanism of CircTHBS1 in CG, providing a potential biomarker and therapeutic target for human CG.