OBJECTIVE: YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors; differentiating between these roles may depend on the YAP1 phosphorylation pattern. The specific function of YAP1 in B cell acute lymphoblastic leukemia (B-ALL), however, is currently unclear. Thus, in the present study, the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.
METHODS: The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting, quantitative real-time polymerase chain reaction, flow cytometry, immunostaining, and nude mouse subcutaneous tumorigenesis experiments. Gene expression levels of Hippo pathway-related molecules before and after verteporfin (VP) treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.
RESULTS: Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels. YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells; YAP1 was distributed in the nuclei in NALM6 cells. Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase. Before and after VP treatment, the expression of the upstream gene LATS1 was upregulated; its overexpression promoted YAP1-Ser127 phosphorylation. Further, YAP1 was distributed in the plasma.
CONCLUSIONS: LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function; thus, VP, which targets this axis, may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

Breast cancer is a molecularly heterogeneous disease and the most common female malignancy. In recent years, therapy approaches have evolved to accommodate molecular diversity, with a focus on more biologically based therapies to minimize negative consequences. To regulate cell fate in human breast cells, the Hippo signaling pathway has been associated with the alpha subtype of estrogen receptors. This pathway regulates tissue size, regeneration, and healing, as well as the survival of tissue-specific stem cells, proliferation, and apoptosis in a variety of organs, allowing for cell differentiation. Hippo signaling is mediated by the kinases MST1, MST2, LATS1, and LATS2, as well as the adaptor proteins SAV1 and MOB. These kinases phosphorylate the downstream effectors of the Hippo pathway, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ), suppressing the expression of their downstream target genes. The Hippo signaling pathway kinase cascade plays a significant role in all cancers. Understanding the principles of this kinase cascade would prevent the occurrence of breast cancer. In recent years, small noncoding RNAs, or microRNAs, have been implicated in the development of several malignancies, including breast cancer. The interconnections between miRNAs and Hippo signaling pathway core proteins in the breast, on the other hand, remain poorly understood. In this review, we focused on highlighting the Hippo signaling system, its key parts, its importance in breast cancer, and its regulation by miRNAs and other related pathways.

Colorectal cancer (CRC) is a common malignancy with significant prevalence and mortality rates. Circular RNA FOXO3 (circ‑FOXO3; hsa_circ_0006404) has been reported to be involved in cancer regulation; however, its role in CRC is yet to be fully elucidated. Therefore, the aim of the present study was to investigate the effect of circ‑FOXO3 on CRC progression and identify its underlying mechanism. In the present study, the expression of circ‑FOXO3 was investigated in CRC tissues and cells via reverse transcription‑quantitative PCR. A Cell Counting Kit‑8 and colony formation assays were used to assess cell proliferation. The cell migratory and invasive abilities were detected using the Transwell migration and invasion assays. The luciferase assay and RNA pull‑down assay were conducted to verify the relationship of circ‑FOXO3, microRNA (miR)‑543 and Large tumor suppressor kinase 1 (LATS1). The results demonstrated that circ‑FOXO3 expression was downregulated in CRC tissues and cells, and was associated with poor overall survival of patients with CRC. Moreover, circ‑FOXO3 was associated with tumor size, distant metastasis, differentiation, lymph node metastasis and TMN stages of patients with CRC. circ‑FOXO3 overexpression suppressed CRC cell proliferation, migration and invasion. Luciferase assay and RNA pull‑down assay results indicated that circ‑FOXO3 functioned as a sponge for miR‑543. In addition, circ‑FOXO3 increased the expression of LATS1 via sponging miR‑543, thus inhibiting CRC cell aggressive features. Collectively, the present results suggested that circ‑FOXO3 inhibited CRC metastasis and progression via elevated LATS1 expression by sponging miR‑543. Therefore, circ‑FOXO3 may be a promising target for CRC therapy.