Fang Liu

Honokiol regulates ovarian cancer cell malignant behavior through YAP/TAZ pathway modulation

AbstractBackgroundOvarian cancer (OVCA) stands as one of the most fatal gynecological malignancies. Honokiol (HNK) has been substantiated by numerous studies for its anti‐tumor activity against malignancies including OVCA. Consequently, this work was designed to elucidate the impact of HNK‐mediated modulation of the YAP/TAZ pathway on the biological functions of OVCA cells.MethodsOVCA cells were subjected to treatment with varying concentrations (0, 25, 50, 75, and 100 μM) of HNK, concomitant with the administration of YAP agonist (XMU). Assessment of cellular viability was executed employing the CCK‐8 assay, while quantification of cellular proliferation transpired via colony formation assays. Apoptosis was ascertained using flow cytometry, and expression of apoptosis‐related proteins (caspase‐3, Bcl‐2, Bax), EMT‐related proteins (E‐cadherin, N‐cadherin), migration‐associated proteins (MMP‐2, MMP‐9), and YAP/TAZ pathway‐related proteins was evaluated by western blot. Transwell experiments were conducted to assess cellular migratory and invasive propensities. Xenograft tumor models were built to observe tumor growth (volume and weight), apoptosis was assessed by TUNEL staining, and Ki67 expression was evaluated through IHC.ResultsHNK exerted inhibitory effects on the viability and proliferative capacity of OVCA cells, elicited apoptotic responses, curtailed the migratory and invasive tendencies of cells, and downregulated the YAP/TAZ pathway. Stimulation with YAP agonist (XMU‐MP‐1) partially attenuated the impacts of HNK on OVCA cell biology. Experiments in vivo confirmed that HNK inhibited OVCA tumor growth.ConclusionThe outcomes of this investigation conclusively established that HNK orchestrated the modulation of the YAP/TAZ pathway, thereby exerting control over the malignant phenotypic manifestations of OVCA cells. The ascertained function of HNK in restraining cellular proliferation and tumor progression provided novel evidence of its anti‐proliferative activity within OVCA cells.

Honokiol induces ferroptosis in ovarian cancer cells through the regulation of YAP by OTUB2

AbstractBackgroundOvarian cancer (OVCA) is prevalent in female reproductive organs. Despite recent advances, clinical outcomes remain poor, warranting fresh treatment avenues. Honokiol has an inhibitory effect on proliferation, invasion, and survival of cancer cells in vitro and in vivo. Therefore, this study intended to explore specific molecular mechanism by which honokiol affected OVCA progression.MethodsBioinformatics analyzed the drug honokiol that bound to OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2). Cellular thermal shift assay (CETSA) verified the binding relationship between honokiol and OTUB2. Cell counting kit 8 (CCK‐8) tested the IC50 value and cell viability of OVCA cells after honokiol treatment. Corresponding assay kits determined malonic dialdehyde (MDA) and Fe2+ levels in OVCA cells. Flow cytometry measured reactive oxygen species levels. Western blot detected OTUB2, SLC7A11, and transcriptional co‐activators Yes‐associated protein (YAP) expression, and quantitative polymerase chain reaction (qPCR) detected OTUB2 expression. Immunohistochemistry (IHC) detected the expression level of Ki67 protein in tumor tissues.ResultsHonokiol was capable of inducing ferroptosis in OVCA cells. CETSA confirmed that honokiol could bind to OTUB2. Further cell functional and molecular experiments revealed that honokiol induced ferroptosis in OVCA cells via repression of YAP signaling pathway through binding to OTUB2. In addition, in vivo experiments have confirmed that honokiol could inhibit the growth of OVCA.ConclusionHonokiol induced ferroptosis in OVCA cells via repression of YAP signaling pathway through binding to OTUB2, implicating that OTUB2 may be an effective target for OVCA treatment, and our study results may provide new directions for development of more effective OVCA treatment strategies.

LncRNA LIFR‐AS1 overexpression suppressed the progression of serous ovarian carcinoma

AbstractBackgroundSerous ovarian carcinoma (SOC) is a common malignant tumor in female reproductive system. Long noncoding RNA (lncRNA) LIFR‐AS1 is a tumor suppressor gene in colorectal cancer, but its effect and underlying mechanism in SOC are still unclear. Therefore, this study focuses on unveiling the regulatory mechanism of LIFR‐AS1 in SOC.MethodsThe relationship between LIFR‐AS1 expression and prognosis of SOC patients was analyzed by TCGA database and Starbase, and then, the LIFR‐AS1 expression in SOC tissues and cells was detected by quantitative real‐time PCR (qRT‐PCR) and in situ hybridization (ISH). Besides, the relationship between LIFR‐AS1 and clinical characteristics was analyzed. Also, the effects of LIFR‐AS1 on the biological behaviors of SOC cells were measured by Cell Counting Kit‐8, colony formation, and wound‐healing and Transwell assays, respectively. Western blot and qRT‐PCR were employed to determine the protein expressions of genes related to proliferation (PCNA), apoptosis (cleaved caspase‐3), epithelial‐mesenchymal transition (E‐cadherin, N‐cadherin, and Snail).ResultsLIFR‐AS1 was lowly expressed in SOC, which was correlated with the poor prognosis of SOC patients. Low expression of LIFR‐AS1 in SOC was associated with the tumor size, clinical stage, lymph node metastasis, and distant metastasis. LIFR‐AS1 overexpression promoted the expressions of cleaved caspase‐3 and E‐cadherin while suppressing the malignant behaviors (proliferation, migration, and invasion) of SOC cells, the expressions of PCNA, N‐cadherin, and Snail. Besides, silencing LIFR‐AS1 exerted the effects opposite to overexpressed LIFR‐AS1.ConclusionLIFR‐AS1 overexpression inhibits biological behaviors of SOC cells, which may be a new therapeutic method.