bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2020‒07‒05
nine papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

  1. Cancer Cell Int. 2020 ;20 274
    Jiang Y, Li W, Yan Y, Yao X, Gu W, Zhang H.
      Background: Radioresistance is an obstacle to limit efficacy of radiotherapy. Meanwhile, long non-coding RNAs (lncRNAs) have been reported to affect radioresistance. Here, we aimed to investigate lncRNAs involving radioresistance development of clear cell renal cell carcinoma (ccRCC), the most frequent type of renal cell carcinoma (RCC).Methods: The mRNA and protein expressions of genes were measured via qRT-PCR and western blot. The relationships among genes were verified by RIP and luciferase reporter assay. The radioresistance of ccRCC cells was evaluated through clonogenic survival assay, MTT assay and TUNEL assay.
    Results: LINC01094 was over-expressed in ccRCC cell lines. LINC01094 expression was increased along with the radiation exposure time and the final stable level was 8 times of the initial level. Knockdown of LINC01094 resulted in enhanced radiosensitivity of ccRCC cells. Mechanically, LINC01094 was a ceRNA of CHEK2 by sponging miR-577. Also, the enhancement of LINC01094 on ccRCC radioresistance was mediated by CHEK2-stabilized FOXM1 protein.
    Conclusion: LINC01094 facilitates ccRCC radioresistance by targeting miR-577/CHEK2/FOXM1 axis, blazing a new trail for overcoming radioresistance in ccRCC.
    Keywords:  CHEK2; FOXM1; LINC01094; ccRCC radio-resistance; miR-577
  2. Onco Targets Ther. 2020 ;13 5857-5868
    Lv D, Xiang Y, Yang Q, Yao J, Dong Q.
      Purpose: Clear cell renal cell carcinoma (ccRCC) is a common urological carcinoma in adults. Long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been reported to be involved in the progression of diverse human cancers, including renal cell carcinoma (RCC). However, the biological mechanism of TUG1 was rarely reported in ccRCC.Methods: The levels of TUG1, microRNA miR-31-5p and flotillin 1 (FLOT1) in ccRCC tissues and cells were detected by qRT-PCR. The interactions between miR-31-5p and TUG1 or FLOT1 were predicted by starBase v2.0 and TargetScan, respectively, which were further validated by RIP assay and RNA pull-down assay. Cell counting kit-8 (CCK-8), flow cytometry and Western blot were used to assess the effects of TUG1 on cell viability, apoptosis rate and the relative protein expression levels in ccRCC cells. In addition, the xenograft tumor assay was conducted to further verify the functions of TUG1 in ccRCC in vivo.
    Results: TUG1 was dramatically up-regulated in ccRCC tissues and cells. TUG1 silencing inhibited cell proliferation and promoted cell apoptosis, autophagy in 786-0 and A498 cells. In addition, TUG1 depletion repressed tumor growth in vivo. Moreover, miR-31-5p was validated as a direct target of TUG1, and microRNA miR-31-5p inhibitor mitigated the effects of TUG1 knockdown on ccRCC progression. Furthermore, FLOT1 was verified to be negatively interacted with miR-31-5p. FLOT1 overexpression attenuated miR-31-5p-mediated inhibitory effect on cell proliferation and promotion effects on cell apoptosis, autophagy. The restoration experiment implicated that TUG1 positively modulated FLOT1 expression by sponging miR-31-5p.
    Conclusion: All data demonstrated that TUG1 promotes cell proliferation and inhibits cell apoptosis and autophagy in ccRCC by miR-31-5p/FLOT1 axis, which may provide a therapeutic target for ccRCC patients.
    Keywords:  FLOT1; clear cell renal cell carcinoma; lncRNA TUG1; miR-31-5p; tumor progression
  3. Inflammation. 2020 Jul 03.
    Cai R, Jiang J.
      Diabetic nephropathy (DN), characterized by glomerular injury, is a common complication of both type 1 and type 2 diabetes, accompanied by massive proteinuria. Podocytes are reported to play pivotal roles in maintaining the glomerular filtration barrier. In addition, the expression of long non-coding RNAs (lncRNAs) ANRIL was upregulated in type 2 diabetes patients. Hence, the aim of this study was to investigate the underlying mechanisms implicated the role of LncRNA ANRIL in podocyte injury in DN. The concentration of inflammatory cytokines was quantified by the corresponding enzyme-linked immunosorbent assay (ELISA) kits. The mRNA levels of the target gene were determined by reverse transcription and real-time quantitative PCR (RT-qPCR). The expressions of proteins were evaluated by Western blot. The activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) level were measured by corresponding commercial kits. Finally, the apoptosis of podocytes was analyzed by TUNEL assay. In our study, LncRNA ANRIL was highly expressed in high glucose (HG)-induced podocytes. Moreover, LncRNA ANRIL silencing attenuated HG-induced inflammation, oxidative stress, and apoptosis and induced MME overexpression in podocytes. Interestingly, MME knockdown abolished the suppressive effect of LncRNA ANRIL silencing on HG-induced inflammation, oxidative stress, and apoptosis in podocytes. LncRNA ANRIL silencing alleviates HG-induced inflammation, oxidative stress, and apoptosis via upregulation of MME in podocytes. Hence, LncRNA ANRIL may be a novel and effective target to ameliorate podocyte injury in DN.
    Keywords:  LncRNA ANRIL; diabetic nephropathy (DN); high glucose (HG); membrane metallo-endopeptidase (MME); podocytes
  4. J Mol Histol. 2020 Jul 01.
    Zhang M, Lu W, Huang Y, Shi J, Wu X, Zhang X, Jiang R, Cai Z, Wu S.
      In the original article, we realized that an error occurred when we grouped the separate photos to generate the combined Figure 4 The same image was accidentally pasted twice in one figure, while we were not fully aware of the error at that time. We immediately reviewed the original data again and made sure that no changes need to be made in other parts of the paper. We are sure that the published manuscript was published without prior knowledge of the error and that it does not alter the conclusions of the study.
  5. Mol Biol Rep. 2020 Jun 29.
    Singh D, Khan MA, Siddique HR.
      Chemotherapy is one of the important treatment modules in early as well as advanced stages of cancer. However, the major limitation of chemotherapy is the development of chemoresistance in the transformed cells of cancer patients, which leads to cancer recurrence. Long non-coding RNAs (lncRNA) are the transcripts longer than 200 nucleotides in length, which are reported to associate with the initiation, progression, recurrence, and metastasis of different cancers. Several lncRNAs have been implicated in the prevalence of chemoresistant phenotypes and also in the restoration of drug sensitivity in chemoresistant cells. LncRNAs such as HOTAIR, H19, and a lot more are involved in the chemoresistance of cancer cells. Therefore, targeting the lncRNAs may serve as a novel strategy for treating chemoresistant cancer. This review throws light on the role of lncRNA in chemoresistance along with the perspective of the therapeutic targets for the treatment of multiple cancers.
    Keywords:  Cancer; Chemoresistance; LncRNA; Signalling pathways; Therapeutic challenges
  6. Cancer Metastasis Rev. 2020 Jun 27.
    Peng Y, Tang D, Zhao M, Kajiyama H, Kikkawa F, Kondo Y.
      Chemotherapy is one of the important and effective options for cancer treatment in the past decades. Although the response rate of initial chemotherapy is considerably high in certain types of cancers, such as ovarian cancer and lung cancer, the patients frequently suffer from chemoresistance and recurrence of disease. Recent genome-wide studies have shown that the large number of long non-coding RNAs (lncRNAs) are transcribed from the human genome and involved in many biological processes including carcinogenesis. They aberrantly regulate variety of cell functions, such as cell cycle, apoptosis, autophagy, and metabolisms, which are associated with chemosensitivity. Therefore, understanding the biological and clinical impacts of lncRNAs on tumor behavior and its potential as a predictive biomarker for chemotherapy effectiveness is highly desired. In this review, we classify the major mechanisms of lncRNA-related chemoresistance and provide theoretical evidences for targeting lncRNAs in certain types of cancers that may open up new therapeutic paradigm for cancer treatment.
    Keywords:  Cancer; Chemoresistance; Epigenetics; Long non-coding RNA
  7. Cancer Res. 2020 Jul 01. 80(13): 2718-2719
    Banday AR, Papenberg BW, Prokunina-Olsson L.
      Long noncoding RNAs (lncRNA) have been implicated in many diseases, including cancer. Although these disease-associated effects have been mostly attributed to the ability of lncRNAs to function as regulatory noncoding transcripts, there is growing evidence that lncRNAs may also encode functional micropeptides. In the current issue of Cancer Research, Wu and colleagues report a micropeptide encoded by a Y chromosome-linked lncRNA that may explain the higher incidence of esophageal cancer in male smokers. Furthermore, this report provides broader insights related to the molecular epidemiology of male-dominant and smoking-driven cancers and may also help explain some cancer-related associations with mosaic Y chromosome loss.See related article by Wu et al., p. 2790.
  8. Br J Biomed Sci. 2020 Jul 02. 1-5
    Ali MA, Shaker OG, Khalefa AA, Abdelwahed MY, Ali E, Ezzat EM, Elghobary HA, Awaji AA, Fouad NA, Ayoub SE.
      BACKGROUND: Systemic Lupus Erythematous (SLE) is a chronic systemic autoimmune disorder whose diagnosis depends on combination of multiple factors. Circulating lncRNAs could serve as diagnostic non-invasive biomarkers for SLE. We hypothesised that serum FAS-AS1 and PVT1 are new biomarkers for SLE that relate to clinical features and laboratory markers.MATERIALS AND METHOD: Measurement of serum FAS-AS1 & PVT1 by qRT-PCR, analysis of the association between two RNAs and the clinical data, activity index and laboratory markers by standard routine methods.
    RESULTS: There was a significant relative increased serum FAS-AS1 (median (IQR) 2.19 (0.13-8.62) and a significant reduced PVT1 (median (IQR) 0.52 (0.01-7.55) in SLE patients compared to controls (P < 0.0001 for FAS-AS1 and = 0.007 for PVT1). Serum FAS-AS1 and PVT1 were positively correlated (r= 0.37, P = 0.001). Higher FAS-AS1 was significantly linked with nephritis (P = 0.011), positive anti-dsDNA (P= 0.01) and lower serum PVT1 was significantly associated with oral ulcers (P= 0.023), photosensitivity (P= 0.017), and neurological manifestations (P= 0.041). Serum PVT1 negatively correlated with age (r= -0.52, P< 0.0001) and ESR level (r= -0.29, P= 0.011) in SLE patients. No correlation between disease activity and serum FAS-AS1 or PVT1 was detected.
    CONCLUSIONS: Our study provides evidence that serum FAS-AS1 and PVT1 are new biomarkers for SLE.
    Keywords:  FAS-AS1; PVT1; qRT-PCR; SLE; Systemic Lupus Erythematous
  9. Neoplasma. 2020 Jul 02. pii: 191023N1081. [Epub ahead of print]
    Yang H, Guo JF, Zhang ML, Li AM.
      Long non-coding RNAs (lncRNAs) have been demonstrated to act as essential regulators in the growth and progression of neuroblastoma. In the present research, the high expression of lncRNA small nucleolar RNA host gene 4 (SNHG4) in neuroblastoma was tested via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and then the function of SNHG4 was explored and verified by CCK-8 assay, EdU assay, cell cycle assay, cell apoptosis test, wound healing test and invasion test in neuroblastoma cell lines. It was discovered that lncRNA SNHG4 exhibited high expression in neuroblastoma tissues and cell lines, and the expression of SNHG4 was associated with the survival of neuroblastoma patients. Additionally, SNHG4 decrement markedly repressed neuroblastoma cells to proliferate and stimulate their apoptosis in vivo and in vitro. Moreover, SNHG4 decrement impeded the abilities of SH-SY5Y and IMR-32 cells to migrate and invade as well as epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG4 acted as a competing endogenous RNA to sponge miR-377-3p, which was downregulated in neuroblastomas and inhibited cell proliferation and invasion. The findings manifested that SNHG4 was inversely associated with miR-377-3p expression in neuroblastoma cases. Collectively, we revealed the functions of SNHG4 and miR-377-3p in neuroblastoma.