The RPS6KA6 gene encodes the p90 ribosomal S6 kinase-4 (RSK4) that is still largely uncharacterized. In this study we identified a new RSK4 transcription initiation site and several alternative splice sites with a 5’RACE approach. The resulting mRNA variants encompass four possible first start codons. The first 15 nucleotides (nt) of exon 22 in mouse and the penultimate exon in both human (exon 21) and mouse (exon 24) RSK4 underwent alternative splicing, although the penultimate exon deleted variant appeared mainly in cell clines, but not in most normal tissues. Demethylation agent 5-azacytidine inhibited the deletion of the penultimate exon whereas two indolocarbazole-derived inhibitors of cyclin dependent kinase 4 or 6 induced deletion of the first 39 nt from exon 21 of human RSK4. In all human cancer cell lines studied, the 90-kD wild type RSK4 was sparse but, surprisingly, several isoforms at or smaller than 72-kD were expressed as detected by seven different antibodies. On immunoblots, each of these smaller isoforms often appeared as a duplet or triplet and the levels of these isoforms varied greatly among different cell lines and culture conditions. Cyclin D1 inhibited RSK4 expression and serum starvation enhanced the inhibition, whereas c-Myc and RSK4 inhibited cyclin D1. The effects of RSK4 on cell growth, cell death and chemoresponse depended on the mRNA variant or the protein isoform expressed, on the specificity of the cell lines, as well as on the anchorage-dependent or -independent growth conditions and the in vivo situation. Moreover, we also observed that even a given cDNA might be expressed to multiple proteins; therefore, when using a cDNA, one needs to exclude this possibility before attribution of the biological results from the cDNA to the anticipated protein. Collectively, our results suggest that whether RSK4 is oncogenic or tumor suppressive depends on many factors.

Breast cancer has been ranked the first malignant tumor in women, and with the incidence of it increasing all over the world, early screening can effectively reduce mortality and improve the cure rate. MiRNAs, as potential biomarkers, play an important role in the early diagnosis and prognosis monitoring of breast cancer. However, since miRNAs, with low concentration, are the matrix in serum or plasma, accurately detecting miRNAs without a label in serum or plasma is challenging. Herein, we proposed a biosensor combination of nanomaterial for reduced graphene oxide (RGO) and field effect transistors (FETs). The biosensor used a few layers of RGO by the chemical reduction method as a semiconductor to detect the miRNA21 in human plasma with high sensitivity (LOD: 1 fM). It can not only distinguish between perfectly matched, single-base mismatched, and completely mismatched sequences, but it can also correctly respond to clinically complex matrix samples without the process of miRNA21 extraction, amplification, and labeling. The area under the receiver operating characteristic (ROC) curve was 0.9253, which means that the biosensor can distinguish between the breast cancer patients and healthy controls and can assist in clinical diagnosis and provide new ideas for the development of clinical testing.

Corporate social responsibility (CSR) has been seen as an effective strategy that emerging market multinational enterprises increasingly adopt in order to cope with the liability of origin, yet much less attention has been paid to the micro-foundations of such a strategy. It remains less explored as to how CSR is leveraged by individuals—that is, expatriates. Addressing this research gap, a total of 150 valid survey responses from 38 Chinese multinationals were tested using the structural equation modeling technique. The results show that expatriates’ cross-cultural competence and engagement in CSR facilitate the learning efficiency of subsidiaries. The findings also suggest that expatriates’ effort positively mediates the relationship between CSR and performance outcomes (at both individual level and organizational level). Embracing the micro-foundations perspective in CSR research, this study offers both theoretical and practical implications for future international management research.

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