Search

Endocytosis of cell surface receptors is essential for cell migration and cancer metastasis. Rab5, a small GTPase of the Rab family, is a key regulator of endosome dynamics and thus cell migration. However, how its activity is regulated still remains to be addressed. Here, we identified a Rab5 inhibitor, a long non-coding RNA, namely HITT (HIF-1α inhibitor at translation level). Our data show that HITT expression is inversely associated with advanced stages and poor prognosis of lung adenocarcinoma patients with area under receiver operating characteristics (ROC) curve (AUC) 0.6473. Further study reveals that both endogenous and exogenous HITT inhibits single-cell migration by repressing β1 integrin endocytosis in lung adenocarcinoma. Mechanistically, HITT is physically associated with Rab5 at switch I via 1248-1347 nt and suppresses β1 integrin endocytosis and subsequent cancer metastasis by interfering with guanine nucleotide exchange factors (GEFs) for Rab5 binding. Collectively, these findings suggest that HITT directly participates in the regulation of Rab5 activity, leading to a decreased integrin internalization and cancer metastasis, which provides important insights into a mechanistic understanding of endocytosis and cancer metastasis.

Understanding how the morphology of a nanocatalyst tailors its catalytic performance is a crucial issue for the rational design and fabrication of active heterogeneous catalysts at the nanometer level. Herein, we demonstrate novel findings of peroxydisulfate (S2O82−; PDS) activation catalyzed by nickel oxide (NiO) nanocatalysts of different morphologies, in which oxygen vacancies (VO) were the defective sites that facilitated the chemical bonding with PDS molecules and promoted the reactivity of VO-connected nickel ions for PDS activation, thus elucidating the structural origin of its catalytic activities. The morphologically tunable NiO with various VO concentrations exhibited different catalytic performance for the removal of phenol (a model organic pollutant). Based on an electron paramagnetic resonance (EPR) study, radical competition reactions, and quenching tests, the main reactive species was revealed to be the non-radical PDS-NiO complex, which can effectively attack C6H5O− to yield intermediates attached to NiO surface. This work not only improves the fundamental understanding of active sites in morphologically tunable transition metal oxides, but also provides valuable guidelines for the rational design and synthesis of high-performance, morphology-dependent nanocatalysts.

Carboxymethyl chitosan (NOCC) with different molecular weight (Mw) and degree of substitution (DS) was synthesized under heterogeneous conditions. The synthesized NOCC was employed as builders in removing unfixed dyes from reactive cotton dyeings. The factors influencing wash-off effectiveness, including the achievable Mw and DS of NOCC and the initial pH value of washing liquor, were investigated. NOCC with the Mw of 25.0 kDa and the DS of approximately 1.0 has achieved the best wash-off effectiveness at the same wash-off conditions. The wash-off effectiveness of NOCC increases with the increase of pH values of washing liquor. The wash-off mechanism was also discussed by spectroscopic study. This study concludes that NOCC is a potential candidate for removing the unfixed reactive dyes on cotton fabrics.

Summary Reactive oxygen species (ROS) have emerged as important signaling molecules that play crucial roles in carcinogenesis and cytotoxic responses. Nrf2 is the master regulator of ROS balance. Thus, uncovering mechanisms of Nrf2 regulation is important for the development of alternative treatment strategies for cancers. Here, we demonstrate that iASPP, a known p53 inhibitor, lowers ROS independently of p53. Mechanistically, iASPP competes with Nrf2 for Keap1 binding via a DLT motif, leading to decreased Nrf2 ubiquitination and increased Nrf2 accumulation, nuclear translocation, and antioxidative transactivation. This iASPP-Keap1-Nrf2 axis promotes cancer growth and drug resistance both in vitro and in vivo . Thus, iASPP is an antioxidative factor and represents a promising target to improve cancer treatment, regardless of p53 status.