Exosomal circRHCG promotes breast cancer metastasis via facilitating M2 polarization through TFEB ubiquitination and degradation.

Triple-negative breast cancer (TNBC) is a highly aggressive cancer with distant metastasis. Accumulated evidence has demonstrated that exosomes are involved in TNBC metastasis. Elucidating the mechanism underlying TNBC metastasis has important clinical significance. In the present study, exosomes were isolated from clinical specimens and TNBC cell lines. Colony formation, EdU incorporation, wound healing, and transwell assays were performed to examine TNBC cell proliferation, migration, and metastasis. Macrophage polarization was evaluated by flow cytometry and RT-qPCR analysis of polarization markers. A mouse model of subcutaneous tumor was established for assessment of tumor growth and metastasis. RNA pull-down, RIP and Co-IP assays were used for analyzing molecular interactions. Here, we proved that high abundance of circRHCG was observed in exosomes derived from TNBC patients, and increased exosomal circRHCG indicated poor prognosis. Silencing of circRHCG suppressed TNBC cell proliferation, migration, and metastasis. TNBC cell-derived exosomes promoted M2 polarization via delivering circRHCG. Exosomal circRHCG stabilized BTRC mRNA via binding FUS and naturally enhanced BTRC expression, thus promoting the ubiquitination and degradation of TFEB in THP-1 cells. In addition, knockdown of BTRC or overexpression of TFEB counteracted exosomal circRHCG-mediated facilitation of M2 polarization. Furthermore, exosomal circRHCG promoted TNBC cell proliferation and metastasis by facilitating M2 polarization. Knockdown of circRHCG reduced tumor growth, metastasis, and M2 polarization through the BTRC/TFEB axis in vivo. In summary, exosomal circRHCG promotes M2 polarization by stabilizing BTRC and promoting TFEB degradation, thereby accelerating TNBC metastasis and growth. Our study provides promising therapeutic strategies against TNBC.

3D Printed Embedded Metamaterials.

The manufacturing of 3D and conformal metamaterials remains a major challenge. The projection micro-stereolithography 3D printing technology combined with the liquid metal filling method is employed here to fabricate the metamaterials, which are characterized with embedded features that can effectively protect the metal resonance layer from external influence, and integrated molding of macro-micro structures and function-structure. To demonstrate the robustness and flexibility of the proposed method, three types of metamaterials are fabricated: 3D orthogonal split-ring resonator metamaterial, bionic compound eye conformal metamaterial, and a five-layer broadband conformal metamaterial in the form of hemispherical moth-eye, which are costly, tedious, and time consuming in conventional fabrication methods. And the layout of the filling channel is optimized and the polydimethylsiloxane coating post-treatment process is applied to smooth the surface roughness caused by the staircase effect of 3D printing to improve the transmission performance of metamaterial devices. The transmission properties are measured using terahertz time-domain spectroscopy system and the experimental results show that the method proposed in this paper makes metamaterial manufacture no longer limited to complex structures, which effectively expands the application range of metamaterials.

The pseudogene derived long noncoding RNA DUXAP8 promotes gastric cancer cell proliferation and migration via epigenetically silencing PLEKHO1 expression.

Gastric cancer (GC) is the third leading cause of cancer death due to its poor prognosis and limited treatment options. Evidence indicates that pseudogene-derived long noncoding RNAs (lncRNAs) may be important players in human cancer progression, including GC. In this paper, we report that a newly discovered pseudogene-derived lncRNA named DUXAP8, a 2107-bp RNA, was remarkably upregulated in GC. Additionally, a higher level of DUXAP8 expression in GC was significantly associated with greater tumor size, advanced clinical stage, and lymphatic metastasis. Patients with a higher level of DUXAP8 expression had a relatively poor prognosis. Further experiments revealed that knockdown of DUXAP8 significantly inhibited cell proliferation and migration, as documented in the SGC7901 and BGC823 cell lines. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that DUXAP8 could epigenetically suppress the expression of PLEKHO1 by binding to EZH2 and SUZ12 (two key components of PRC2), thus promoting GC development. Taken together, our findings suggest that the pseudogene-derived lncRNA DUXAP8 promotes the progression of GC and is a potential therapeutic target for GC intervention.

KLF16 promotes proliferation in gastric cancer cells via regulating p21 and CDK4.

Krüppel-like factors (KLFs), such as KLF4, KLF2, KLF5 and KLF15, have been extensively investigated in multi-cancers. However, KLF16, a member of KLFs, hasn't been well identified in cancer, especially in gastric cancer (GC). Here, we investigated the roles of KLF16 in GC. In present study, we found that KLF16 expression levels were significantly up-regulated in GC tissues compared to adjacent normal tissues both in protein and mRNA levels by using immunohistochemistry assays (IHC) and real-time quantitative PCR (qPCR). And KLF16 expression levels were positively correlated to tumor size, invasion depth, lymphatic metastasis and TNM stage. Furthermore, KLF16 expression also could predict prognosis in patients with GC. Moreover, the knock-down of KLF16 could significantly suppress proliferation via increasing p21 expression and decreasing CDK4 expression in GC cell lines. In summary, these findings demonstrate that KLF16 plays a significant role in GC progression and could be a new therapeutic target for GC patients.

Long intergenic non-coding RNA 00152 promotes lung adenocarcinoma proliferation via interacting with EZH2 and repressing IL24 expression.

BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown. METHODS: Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24. RESULTS: LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD. CONCLUSIONS: Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.

Long non-coding RNAs in anti-cancer drug resistance.

Chemotherapy is one of the basic treatments for cancers; however, drug resistance is mainly responsible for the failure of clinical treatment. The mechanism of drug resistance is complicated because of interaction among various factors including drug efflux, DNA damage repair, apoptosis and targets mutation. Long non-coding RNAs (lncRNAs) have been a focus of research in the field of bioscience, and the latest studies have revealed that lncRNAs play essential roles in drug resistance in breast cancer, gastric cancer and lung cancer, et al. Dysregulation of multiple targets and pathways by lncRNAs results in the occurrence of chemoresistance. In this review, we will discuss the mechanisms underlying lncRNA-mediated resistance to chemotherapy and the therapeutic potential of lncRNAs in future cancer treatment.

The pseudogene DUXAP10 promotes an aggressive phenotype through binding with LSD1 and repressing LATS2 and RRAD in non small cell lung cancer.

Pseudogenes have been considered as non-functional transcriptional relics of human genomic for long time. However, recent studies revealed that they play a plethora of roles in diverse physiological and pathological processes, especially in cancer, and many pseudogenes are transcribed into long noncoding RNAs and emerging as a novel class of lncRNAs. However, the biological roles and underlying mechanism of pseudogenes in the pathogenesis of non small cell lung cancer are still incompletely elucidated. This study identifies a putative oncogenic pseudogene DUXAP10 in NSCLC, which is located in 14q11.2 and 2398 nt in length. Firstly, we found that DUXAP10 was significantly up-regulated in 93 human NSCLC tissues and cell lines, and increased DUXAP10 was associated with patients poorer prognosis and short survival time. Furthermore, the loss and gain of functional studies including growth curves, migration, invasion assays and in vivo studies verify the oncogenic roles of DUXAP10 in NSCLC. Finally, the mechanistic experiments indicate that DUXAP10 could interact with Histone demethylase Lysine specific demethylase1 (LSD1) and repress tumor suppressors Large tumor suppressor 2 (LATS2) and Ras-related associated with diabetes (RRAD) transcription in NSCLC cells. Taken together, these findings demonstrate DUXAP10 exerts the oncogenic roles through binding with LSD1 and epigenetic silencing LATS2 and RRAD expression. Our investigation reveals the novel roles of pseudogene in NSCLC, which may serve as new target for NSCLC diagnosis and therapy.