RNF6 is a little-studied ring finger protein. In the present study, we found that RNF6 was overexpressed in various leukemia cells and that it accelerated leukemia cell proliferation, whereas knockdown of RNF6 delayed tumor growth in xenografts. To find out the mechanism of RNF6 overexpression in leukemia, we designed a series of truncated constructs of RNF6 regulatory regions in the luciferase reporter system. The results revealed that the region between ؊144 and ؊99 upstream of the RNF6 transcription start site was critical and that this region contained a PBX1 recognition element (PRE). PBX1 modulated RNF6 expression by binding to the specific PRE. When PRE was mutated, RNF6 transcription was completely abolished. Further studies showed that PBX1 collaborated with PREP1 but not MEIS1 to modulate RNF6 expression. Moreover, RNF6 expression could be suppressed by doxorubicin, a major anti-leukemia agent, via down-regulating PBX1. This study thus suggests that RNF6 overexpression in leukemia is under the direction of PBX1 and that the PBX1/RNF6 axis can be developed as a novel therapeutic target of leukemia.The ring finger protein 6 (RNF6) belongs to the largest RING ubiquitin ligase family, and it is mapped to chromosome band 13q12.2, a harbor of several critical tumor suppressor genes (1). RNF6 is believed to be a tumor suppressor because of its chromosomal location and somatic mutations in esophageal squamous cell carcinomas (2), but confirmative evidence is not available. In contrast, recent studies suggest that RNF6 is probably an oncogene. RNF6 is found at a high level in prostate cancers. As a ubiquitin ligase, RNF6 interacts with androgen receptor (AR) 3 and mediates atypical polyubiquitination chains at Lys-6 and Lys-27, thus promoting the transcriptional activity of AR by facilitating its binding to the coactivators (3). By modulating AR function, RNF6 promotes prostate cancer cell growth. In contrast, mutations and specific knockdown of RNF6 alter AR transcriptional activity and delay prostate cancer growth in xenograft models (3). RNF6 is also elevated in cisplatin-resistant human lung adenocarcinoma cells (4). Therefore, RNF6 probably plays a critical role in tumorigenesis and chemoresistance. However, the studies on RNF6 are very limited, and the biological functions and modulation of RNF6 are largely unknown.In the present study, we evaluated the RNF6 function in leukemia cells and found that RNF6 is overexpressed in leukemia cells and contributes to leukemia cell proliferation. Furthermore, RNF6 overexpression in leukemia is found to be modulated by the transcription factor PBX1, the pre-B-cell leukemia homeobox 1.

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Nuclear factor kappa B (NF‐κB) signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. In the present study, we found that the widely used antimalarial drug mefloquine was a NF‐κB inhibitor that blocked the activation of IκBα kinase, leading to reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF‐κB target genes in CRC cells. We also found that mefloquine induced growth arrest and apoptosis of CRC cells harboring phosphorylated p65 in culture and in mice. Furthermore, expression of constitutive active IKKβ kinase significantly attenuated the cytotoxic effect of the compound. These results showed that mefloquine could exert antitumor action through inhibiting the NF‐κB signaling pathway, and indicated that the antimalarial drug might be repurposed for anti‐CRC therapy in the clinic as a single agent or in combination with other anticancer drugs.

Clioquinol is an anti-microbial drug, and it was recently found to induce cancer cell death. In the present study, clioquinol was found to trigger autophagy by inducing LC3 lipidation and autophagosome formation which was abolished by an autophagy inhibitor 3-methyladenine. Further study showed clioquinol displayed no effects on PI3KC3 or Beclin 1 expression but downregulated the expression and the enzymatic activity of mammalian target of Rapamycin (mTOR), a critical modulator of autophagy. Moreover, clioquinol inhibited the catalytic activity of the mTOR complex 1, thus suppressing phosphorylation of P70S6K and 4E-BP1, two major proteins associated with autophagy in the mTORC1 signaling pathway. Clioquinol induced leukemia and myeloma cell apoptosis, however, addition of autophagy inhibitor 3-methyladenine attenuated this kind of cell death. Therefore, this study demonstrated that clioquinol induces autophagy in associated with apoptosis in leukemia and myeloma cells by disrupting mTOR signaling pathway.

In duty-cycled wireless sensor networks, the nodes switch between active and dormant states, and each node may determine its active/dormant schedule independently. This complicates the Minimum-Energy Multicasting (MEM) problem, which has been primarily studied in always-active wireless adhoc networks. In this paper, we study the duty-cycle-aware MEM problem in wireless sensor networks, and we present a formulation of the Minimum-Energy Multicast Tree Construction and Scheduling (MEMTCS) problem. We prove that the MEMTCS problem is NP-hard, and it is unlikely to have an approximation algorithm with a performance ratio of (1 − o(1)) ln ∆, where ∆ is the maximum node degree in a network. We propose a polynomial-time approximation algorithm for the MEMTCS problem with a performance ratio of O(H(∆ + 1)), where H(·) is the harmonic number. We also provide a distributed implementation of our algorithm. Finally, we perform extensive simulations and the results demonstrate that our algorithm significantly outperform other known algorithms in terms of both the total energy cost and the transmission redundancy.