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Background To determine whether and how miR15a/16 regulate TGF-β signaling pathways during the progression of prostate cancer. Methods We used bioinformatics prediction, reporter gene assay, real-time PCR, Matrigel invasion assay and Western blot to dissect the molecular mechanism of how miR-15a/miR-16 may cause metastasis in prostate tumor. Results MiR-15a/16 targeted and inhibited the expression of endogenous Smad3 and ACVR2A proteins. The overexpression of miR15a/16 down-regulated p-smad3 expression, affected the expression of both MMP2 and E-cadherin, and down-regulated the expression of the EMT-mediated factors Snail and Twist in LNCaP prostate cancer cells. The overexpression of miR15a/16 decreased the invasion of LNCaP cells. MiR-15a/miR-16 cluster could reverse the invasion of activin A-mediated prostate cancer cells. After the inhibition of the activin/smad signaling pathway, the inhibitory effect of invasion in prostate cancer cells by miR-15a/miR-16 cluster disappeared. Conclusion Our data indicated that miR15a/16 inhibited the components of TGF-β signaling pathways in LNCaP cell line, which might relate to the progression and metastasis of prostate cancer. [ABSTRACT FROM AUTHOR]

Urothelial carcinoma (UC) is a prevalent malignant tumor involving the urinary system. Although there are various treatment modalities, including surgery, chemotherapy, and immune checkpoint inhibitor (ICI) therapy, some patients experience disease recurrence and metastasis with poor prognosis and dismal long-term survival. Antibody–drug conjugates (ADCs), which combine the targeting ability of antibody drugs with the cytotoxicity of chemotherapeutic drugs, have recently emerged as a prominent research focus in the development of individualized precision cancer therapy. Although ADCs have improved the overall response rate in patients with UC, their effectiveness remains limited. Currently, ADC-based combination therapies, particularly ADC combined with ICIs, have demonstrated promising efficacy. This combination approach has advanced the treatment of UC, exhibiting the potential to become the standard first-line therapy for advanced UC in the future. This article reviewed clinical trials involving ADC-based combination therapy for UC and discussed the possible challenges and future perspectives to provide guidance for the clinical treatment of UC. • ADCs in combination with ICIs have demonstrated remarkable effects. • Clinical studies of ADCs combined therapy may provide new suggestion for UC. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A), as the most abundant and well-known RNA modification, has been found to play an important role in cancer. Circular RNAs (circRNAs) are a class of single-stranded covalently closed RNA molecules generated by the reverse splicing process. Recent studies have revealed the vital roles of circRNAs in many diseases, including tumorigenesis. Accumulating evidence also shows an association between m6A modification and circRNAs. This study aimed to review the interactions between m6A modification and circRNAs and illustrate their roles in tumorigenesis. m6A modification can modulate the biogenesis, translation, cytoplasmic export, degradation, and other functions of circRNAs in different tumors. circRNAs can also modulate m6A modification by affecting writers, erasers, and readers. We focused on the potential regulatory mechanisms and the biological consequences of m6A modification of circRNAs, as well as the interactions in tumors of different systems. Finally, we listed the possible development directions of m6A modification and circRNAs, which might facilitate the clinical application of tumor therapy. Not applicable. Keywords • m6A modification could play an important role in the field of oncology. • The regulatory mechanisms and biological functions of m6A modification of circRNAs. • The possible development directions of m6A modification and circRNAs in tumor therapy. [ABSTRACT FROM AUTHOR]