Explore the vast range of titles available.

Background Some circular RNAs (circRNAs) can be translated into functional peptides by small open reading frames (ORFs) in a cap-independent manner. Internal ribosomal entry site (IRES) and N 6 -methyladenosine (m 6 A) were reported to drive translation of circRNAs. Experimental methods confirming the presence of IRES and m 6 A site are time consuming and labor intensive. Lacking computational tools to predict ORFs, IRESs and m 6 A sites for circRNAs makes it harder. Results In this report, we present circPrimer 2.0, a Java based software for annotating circRNAs and predicting ORFs, IRESs, and m6A sites of circRNAs. circPrimer 2.0 has a graphical and a command-line interface that enables the tool to be embed into an analysis pipeline. Conclusions circprimer 2.0 is an easy-to-use software for annotating circRNAs and predicting translation potential of circRNAs, and freely available at www.bio-inf.cn .

Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME) with diverse functions such as extracellular matrix (ECM) remodeling, modulation of metabolism and angiogenesis, and crosstalk with both cancer cells and infiltrating immune cells by production of growth factors, cytokines, and chemokines. Within the TME milieu, CAFs exhibit morphological and functional transitions with relatively specific markers and hold tremendous potential to facilitate tumorigenesis, development, and resistance towards multiple therapeutic strategies including chemotherapy, radiotherapy, targeted therapy, anti-angiogenesis therapy, immunotherapy, and endocrine therapy. Accordingly, CAFs themselves and the downstream effectors and/or signaling pathways are potential targets for optimizing the sensitivity of anti-cancer therapies. This review aims to provide a detailed landscape of the role that CAFs play in conferring therapeutic resistance in different cancers and the underlying mechanisms. The translational and therapeutic perspectives of CAFs in the individualized treatment of malignant tumors are also discussed.

The C-reactive protein-albumin-lymphocyte (CALLY) index has been identified as a useful and sensitive predictive tool for stratification in cancers. This investigation aimed to validate the prognostic ability of CALLY in esophageal squamous cell carcinoma (ESCC). Clinical characteristics of 318 patients with ESCC who underwent radical excision were gathered and analyzed retrospectively. A restricted cubic spline (RCS) model was used to determine an ideal threshold of CALLY due to the non-linear relation. To investigate the predictors, Cox hazard regression analysis was used. The recursive partitioning analysis (RPA), a method of risk categorization, was also developed for prognostic prediction. The receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were used to distinguish from the traditional TNM stage. Patients were compared by groups according to the optimal threshold of CALLY index, which was depicted by the non-linear relation between the cancer-specific survival (CSS) and CALLY index (P < 0.0001). Compared to those with high CALLY index, patients with low CALLY index experienced significantly worse 5-year CSS (21.8% vs. 62.6%, P < 0.001). At different TNM stages, patients with high CALLY index also had better 5-year CSS (I: P = 0.029; II: P < 0.001; III: P < 0.001) in subgroup analyses. The hazard ratio for CSS was 0.368 and CALLY index was an independent predictive factor (P < 0.001). Using TNM stage and CALLY-based RPA algorithms, a new staging was created. The RPA model considerably outperformed the TNM classification for prognostication using ROC (P < 0.001). The DCA also demonstrated that the new model outperformed the TNM stage with significantly improved accuracy for CSS. The prognostic value of CALLY in ESCC undergoing radical resection was initially determined in this study. CALLY was substantially related to prognosis and might be utilized in conjunction with TNM to evaluate ESCC prior to surgery.

Background Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations. Methods We analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them. Results During a median follow-up period of 7.1 years (interquartile range: 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.02 per 1mg/L increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mg/L (false-discovery rate adjust (FDR-adjusted) P overall < 0.001 and FDR-adjusted P non-linear < 0.001). For site-specific cancer, we observed positive linear associations for cancers of esophagus and stomach (FDR-adjusted P overall < 0.050 and FDR-adjusted P non-linear > 0.050). In addition, we also observed three different patterns of non-linear associations, including “fast-to-low increase” (head and neck, colorectal, liver, lung, kidney cancer, and non-Hodgkin lymphoma), “increase-to-decrease” (breast cancer), and “decrease-to-platform” (chronic lymphocytic leukemia). Furthermore, the inflection points of non-linear association patterns were consistently at around 3mg/L. By contrast, there was no evidence for linear or non-linear associations between genetically predicted CRP and risks of overall cancer or site-specific cancers. Conclusions Our results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks.

Background Since circular RNAs (circRNAs) post-transcriptionally regulate gene expression, they have attracted increasing attention. However, there is no existing tool to annotate and extract spliced sequences for circRNAs and no tool to determine the specificity of circRNA primers. Results In this study, we present circPrimer, which allows users to search, annotate, and visualize circRNAs. Additionally, circPrimer enables users to extract the spliced sequences and genomic sequences of any circRNA, including novel circRNAs. Furthermore, circPrimer help users to design primers for circRNAs and to determine the specificity of the circRNA primers. Conclusions CircPrimer is a user-friendly tool for exploring circRNAs that does not require special user skills.

Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100-5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100-5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100-5p. Exosomes confer recipient cells' resistance to DDP in an exosomal miR-100-5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells' sensitivity to DDP in exosomal miR-100-5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer.

Over the past several years, long non‐coding RNAs (lncRNAs) have attracted more and more attention due to their special functions. They are vital biomarkers in multiple diseases. LncRNA HOMEOBOX A11 (HOXA11) has been found to be aberrantly expressed in some kinds of malignant tumors. In this study, we mainly discuss the oncogenic role of it in promoting malignant progression and chemoresistance in lung adenocarcinoma (LUAD) cells. The expression of HOXA11‐AS was much stronger in cisplatin‐resistant LUAD cells. Based on The Cancer Genome Atlas database, patients with high expression of HOXA11‐AS had shorter survival time. Additionally, knockdown of HOXA11‐AS caused positive changes in cell activities of LUAD. For example, cell proliferation and migration were weakened, the epithelial mesenchymal transition process was reversed, and apoptosis was induced. These changes were more obvious in cells treated with cisplatin. Next, the HOXA11‐AS/miR‐454‐3p/Stat3 (signal transducer and activator of transcription 3) pathway was found to influence the cisplatin resistance of LUAD cells. HOXA11‐AS specifically acted as a competing endogenous RNA (ceRNA) in LUAD cells. The combinations among these three genes were demonstrated. Finally, rescue assays were applied to demonstrate the ceRNA pattern consisting of HOXA11‐AS, miR‐454‐3p and Stat3. In conclusion, lncRNA HOXA11‐AS acted as a ceRNA to promote cisplatin resistance of human LUAD cells via the miR‐454‐3p/Stat3 axis. LncRNA HOXA11‐AS has been studied in several kinds of human malignant tumors, while it was not deeply researched in LUAD. In this study, we uncovered a novel pathway (HOXA11‐AS‐miR‐454‐3p‐Stat3), which was proved to be a functional axis in LUAD. We thought the data were adequate and useful. This study might provide a new therapeutic pathway for LUAD.

Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer. High invasiveness and heterogeneity, as well as a lack of drug targets, are the main factors leading to poor prognosis. Brain metastasis (BM) is a serious event threatening the life of breast cancer patients, especially those with TNBC. Compared with that for hormone receptor-positive and HER2-positive breast cancers, TNBC-derived BM (TNBCBM) occurs earlier and more frequently, and has a worse prognosis. There is no standard treatment for BM to date, and one is urgently required. In this review, we discuss the current knowledge regarding the developmental patterns of TNBCBM, focusing on the key events in BM formation. Specifically, we consider (i) the nature and function of TNBC cells; (ii) how TNBC cells cross the blood-brain barrier and form a fenestrated, more permeable blood-tumor barrier; (iii) the biological characteristics of TNBCBM; and (iv) the infiltration and colonization of the central nervous system (CNS) by TNBC cells, including the establishment of premetastatic niches, immunosurveillance escape, and metabolic adaptations. We also discuss putative therapeutic targets and precision therapy with the greatest potential to treat TNBCBM, and summarize the relevant completed and ongoing clinical trials. These findings may provide new insights into the prevention and treatment of BM in TNBC patients.

Cancer immunotherapy is a major breakthrough in the history of tumor therapy in the last decade. Immune checkpoint inhibitors blocking CTLA-4/B7 or PD-1/PD-L1 pathways have greatly prolonged the survival of patients with different cancers. Long non-coding RNAs (lncRNAs) are abnormally expressed in tumors and play an important role in tumor immunotherapy through immune regulation and immunotherapy resistance. In this review, we summarized the mechanisms of lncRNAs in regulating gene expression and well-studied immune checkpoint pathways. The crucial regulatory function of immune-related lncRNAs in cancer immunotherapy was also described. Further understanding of the underlying mechanisms of these lncRNAs is of great importance to the development of taking lncRNAs as novel biomarkers and therapeutic targets for immunotherapy.

EGFR-mutant lung cancer (LC) patients display a poor response to PD-1/PD-L1 blockade. In the absence of independent genetic validation, whether EGFR mutation distorts host antitumor immunity is unknown. Here, we showed that in the clinic, LC with the E746-A750 deletion mutation (EGFR-19del) displayed a temporal association with the loss of intratumoral CD8+ T cells. In a xenograft model, EGFR-19del-expressing Lewis lung cancer (LLC) tumors had a low T cell density at the early stage of tumor development, along with dendritic cells (DCs) exhibiting variant phenotypes in the tumors and draining lymph nodes (LNs). Importantly, EGFR-19del DCs were observed in the LNs of tumor-bearing mice and LC patients. The proliferative activity of T cells within the LN was significantly dampened. In vitro experiments indicated that the function of DCs was repressed by EGFR-19del LLC cells through exosome uptake in which exosomes derived from the EGFR-19del LLC cells could efficiently transfer active EGFR-19del to the surface of the DCs. Injection of EGFR-19del tumor-derived exosomes promoted LLC tumor progression and induced immunosuppression. The combination of gefitinib and GM-CSF treatment recovered tumor T cell infiltration in EGFR-19del tumors by rescuing the function of DCs and increasing the efficacy of anti-PD-L1 treatment. Together, these results indicated that LC with the EGFR E746-A750 deletion mutation induced anergic DCs to repress antitumor immunity through exosomes.