Because of the lack of sensitivity to radiotherapy and chemotherapy, therapeutic options for renal clear cell carcinoma (KIRC) are scarce. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of cancer. However, their functional roles and upstream mechanisms in KIRC remain largely unknown. Exploring the functions of potential essential lncRNAs may lead to the discovery of novel targets for the diagnosis and treatment of KIRC. Here, according to the integrated analysis of RNA sequencing and survival data in TCGA-KIRC datasets, cyclin-dependent kinase inhibitor 2B antisense lncRNA (CDKN2B-AS1) was discovered to be the most upregulated among the 14 lncRNAs that were significantly overexpressed in KIRC and related to shorter survival. Functionally, CDKN2B-AS1 depletion suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, CDKN2B-AS1 exerted its oncogenic activity by recruiting the CREB-binding protein and SET and MYND domain-containing 3 epigenetic-modifying complex to the promoter region of Ndc80 kinetochore complex component (NUF2), where it epigenetically activated NUF2 transcription by augmenting local H3K27ac and H3K4me3 modifications. Moreover, we also showed that CDKN2B-AS1 interacted with and was stabilized by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal protein showing increased levels in KIRC. The Kaplan–Meier method and receiver operating curve analysis revealed that patients whose IGF2BP3, CDKN2B-AS1 and NUF2 are all elevated showed the shortest survival time, and the combined panel (containing IGF2BP3, CDKN2B-AS1, and NUF2) possessed the highest accuracy in discriminating high-risk from low-risk KIRC patients. Thus, we conclude that the stabilization of CDKN2B-AS1 by IGF2BP3 drives the malignancy of KIRC through epigenetically activating NUF2 transcription and that the IGF2BP3/CDKN2B-AS1/NUF2 axis may be an ideal prognostic and diagnostic biomarker and therapeutic target for KIRC.
As
a kind of biocompatible material with long history, silk fibroin
is one of the ideal platforms for on-skin and implantable electronic
devices, especially for self-powered systems. In this work, to solve
the intrinsic brittleness as well as poor chemical stability of pure
silk fibroin film, mesoscopic doping of regenerated silk fibroin is
introduced to promote the secondary structure transformation, resulting
in huge improvement in mechanical flexibility (∼250% stretchable
and 1000 bending cycles) and chemical stability (endure 100 °C
and 3–11 pH). Based on such doped silk film (SF), a flexible,
stretchable and fully bioabsorbable triboelectric nanogenerator (TENG)
is developed to harvest biomechanical energy in vitro or in vivo for
intelligent wireless communication, for example, such TENG can be
attached on the fingers to intelligently control the electrochromic
function of rearview mirrors, in which the transmittance can be easily
adjusted by changing contact force or area. This robust TENG shows
great potential application in intelligent vehicle, smart home and
health care systems.
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