<p>Paclitaxel Suppresses Hepatocellular Carcinoma Tumorigenesis Through Regulating Circ-BIRC6/miR-877-5p/<em>YWHAZ</em> Axis</p>

Abstract

Background: Paclitaxel is an effective chemotherapeutic agent for the treatment of cancer patients. Accumulating evidence suggests that circular RNAs (circRNAs) play critical roles in the occurrence and development of human cancers. However, there are few studies on interactions between paclitaxel and circRNAs in hepatocellular carcinoma (HCC). Materials and Methods: Cell counting kit-8 (CCK-8) assay and colony formation assay were conducted to determine cell proliferation. Cell apoptosis was assessed by flow cytometry. The expression levels of circRNA baculoviral IAP repeat-containing 6 (circ-BIRC6), microRNA-877-5p (miR-877-5p), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta (YWHAZ) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mice xenograft model was established to investigate the roles of circ-BIRC6 and paclitaxel in vivo. The interaction between miR-877-5p and circ-BIRC6 or YWHAZ was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. Western blot assay was applied for measuring the protein expression of YWHAZ. Results: Paclitaxel suppressed HCC tumorigenesis through decreasing cell proliferation and accelerating apoptosis. Circ-BIRC6 and YWHAZ were upregulated, and miR-877-5p was downregulated in HCC tissues and cells. Paclitaxel treatment inhibited the expression of circ-BIRC6 and YWHAZ while promoted the expression of miR-877-5p. Circ-BIRC6 overexpression or miR-877-5p interference reversed the inhibitory effect of paclitaxel on HCC tumorigenesis. Moreover, miR-877-5p could specially bind to YWHAZ, and its knockdown abated the suppressive effect of circ-BIRC6 depletion on HCC tumorigenesis. Additionally, YWHAZ was identified as a direct target of miR-877-5p. Besides, circ-BIRC6 functioned as a molecular sponge of miR-877-5p to regulate YWHAZ expression. Conclusion: Paclitaxel limited HCC tumorigenesis via modulating circ-BIRC6/miR-877-5p/YWHAZ axis, providing a novel therapeutic approach for the treatment of HCC.

Lnc524369 promotes hepatocellular carcinoma progression and predicts poor survival by activating YWHAZ-RAF1 signaling

“…YWHAZ has been shown to be commonly upregulated in multiple cancers, especially HCC, as it can promote tumorigenesis, metastasis, and chemoresistance in the progression of cancer[ 19 - 21 ]. Our bioinformatic analysis showed that RAF1 was strongly coexpressed with YWHAZ (Figure 3E ).…”

Construction and Comprehensive Analysis of a circRNA-miRNA-mRNA Regulatory Network to Reveal the Pathogenesis of Hepatocellular Carcinoma

“…Evidence showed that increased LOX could promote angiogenesis, induce epithelial-mesenchymal transition, and is related to early recurrence of HCC ( Umezaki et al, 2019 ; Yang et al, 2019 ). Furthermore, accumulated evidence has demonstrated that multiple molecules mediated the tumorigenesis and metastasis of HCC by regulating the YWHAZ -associated axis ( Zhao et al, 2018 ; Wei et al, 2019 ; Liu et al, 2020a ; Shen et al, 2020 ). Bioinformatic analysis also revealed the miR-139-5p/ CCT5 axis might exert a momentous effect on HCC progression, but in-depth validated studies have not been carried out ( Xu et al, 2021 ).…”

Circ_0061140 knockdown inhibits tumorigenesis and improves PTX sensitivity by regulating miR-136/CBX2 axis in ovarian cancer

“…Circ_PVT1 repressed gastric cancer resistance to PTX via binding to miR-124-3p [ 28 ]. Circ_BIRC6 overexpression relieved PTX-induced repression of hepatocellular carcinoma progression through trapping miR-877-5p [ 29 ]. Additionally, circ_ZFR promoted PTX resistance in lung cancer in a miR-195-5p-dependent manner [ 30 ].…”