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MicroRNA-21 (miR-21) is associated with the development of solid tumors progression including breast cancer. In this study we investigated matrix hyaluronan (HA)-CD44 (a primary HA receptor) interaction with c-Jun N-Terminal Kinase (JNK)/c-Jun signaling in MDA-MB-468 breast cancer cells [a triple-negative (estrogen receptor-negative/progesterone receptor-negative/HER2-negative) breast cancer cell line]. Our results indicated that HA binding to CD44 promotes c-Jun nuclear translocation and transcriptional activation. Further analyses revealed that miR-21 is regulated by an upstream promoter containing AP1 binding site(s), and chromatin immunoprecipitation (CHIP) assays demonstrated that stimulation of miR-21 expression by HA/CD44 interaction is c-Jun-dependent in these breast cancer cells. This process results in an increase of the anti-apoptosis protein Bcl-2 and upregulation of inhibitors of the apoptosis family of proteins (IAPs) as well as chemoresistance in MDA-MB-468 cells. Treatment with c-Jun specific small interfering RNAs effectively blocks HA-mediated c-Jun signaling and abrogates miR-21 production as well as causes downregulation of survival proteins (Bcl-2 and IAPs) and enhancement of chemosensitivity. In addition, our results demonstrated that anti-miR-21 inhibitor not only downregulates Bcl-2/IAP expression but also increases chemosensitivity in HA-treated breast cancer cells. Together, these findings suggest that the HA/CD44-induced c-Jun signaling plays a pivotal role in miR-21 production leading to survival protein (Bcl-2/IAP) upregulation and chemoresistance in triple negative breast cancer cells such as MDA-MB-468 cell line. This novel HA/CD44-mediated c-Jun signaling pathway and miR-21 production provide a new drug target for the future intervention strategies to treat breast cancer.

A trusted platform module is identified by its endorsement key, while it uses an attestation key to provide attestation services, for example, signing a set of platform configuration registers, providing a timestamp or certifying another of its keys. This paper addresses the problem of how a certificate authority binds the endorsement and attestation keys together. This is necessary for the authority to be able to reliably certify the attestation key. This key binding also enables the authority to revoke the attestation key should the endorsement key be compromised. We study all of the existing solutions and show that they either do not solve the problem or cannot be implemented with a real trusted platform module (or both). We propose a new solution which addresses this problem. We develop a security model for our solution and provide a rigorous security proof under this model. We have also implemented the solution using a real trusted platform module, and our implementation results show that this solution is feasible and efficient. [ABSTRACT FROM AUTHOR]

Group signatures and their variants have been widely used in privacy-sensitive scenarios such as anonymous authentication and attestation. In this paper, we present a new post-quantum group signature scheme from symmetric primitives. Using only symmetric primitives makes the scheme less prone to unknown attacks than basing the design on newly proposed hard problems whose security is less well-understood. However, symmetric primitives do not have rich algebraic properties, and this makes it extremely challenging to design a group signature scheme on top of them. It is even more challenging if we want a group signature scheme suitable for real-world applications, one that can support large groups and require few trust assumptions. Our scheme is based on MPC-in-the-head non-interactive zero-knowledge proofs, and we specifically design a novel hash-based group credential scheme, which is rooted in the SPHINCS+ signature scheme but with various modifications to make it MPC (multi-party computation) friendly. The security of the scheme has been proved under the fully dynamic group signature model. We provide an implementation of the scheme and demonstrate the feasibility of handling a group size as large as 260. This is the first group signature scheme from symmetric primitives that supports such a large group size and meets all the security requirements. [ABSTRACT FROM AUTHOR]

Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer stem cell properties, including self-renewal, clonal formation, and chemotherapy resistance in HA-CD44v3-activated head and neck cancer.