Long noncoding RNAs (lncRNAs) are a relatively well-characterized class of noncoding RNA (ncRNA) molecules, involved in the regulation of various cell processes, including transcription, intracellular trafficking, and chromosome remodeling Their deregulation has been associated with the development and progression of various cancer types, the fact which makes them suitable as biomarkers for cancer diagnosis and prognosis In recent years, detection of cancer-associated lncRNAs in body fluids of cancer patients has proven itself as an especially valuable method to effectively diagnose cancer Cancer diagnosis and prognosis employing circulating lncRNAs are preferential when compared to classical biopsies of tumor tissues, especially due to their noninvasiveness, and have great potential for routine usage in clinical practice Thus, this review focuses on summarizing the perspectives of lncRNAs as biomarkers in cancer, based on evaluating their expression profiles determined in body fluids of cancer patients

/pdf/long-noncoding-rnas-as-biomarkers-in-cancer-2yanbdkasv.pdf

Long Noncoding RNAs as Biomarkers in Cancer.

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.

/pdf/mapk-erk-signaling-pathway-in-hepatocellular-carcinoma-3x8cn125ym.pdf

MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure. One type of ncRNA, called long non-coding RNAs (lncRNAs), has become increasingly recognized as being both highly dysregulated in cancer and to play a variety of different roles in tumourigenesis. Indeed, over the last few years, lncRNAs have rapidly emerged as key regulators of EMT in cancer. In this review, we discuss the lncRNAs that have been associated with the EMT process in cancer and the variety of molecular mechanisms and signalling pathways through which they regulate EMT, and finally discuss how these EMT-regulating lncRNAs impact on both anti-cancer drug resistance and the cancer stem cell phenotype.

https://www.mdpi.com/2072-6694/9/4/38/pdf

Long Non-Coding RNAs: Key Regulators of Epithelial-Mesenchymal Transition, Tumour Drug Resistance and Cancer Stem Cells

P73 antisense RNA 1 T (non-protein coding), also known as TP73-AS1, is a long non-coding RNA (lncRNA) which is involved in cell proliferation and the development of tumors. However, the exact effects and molecular mechanisms of TP73-AS1 in hepatocellular carcinoma (HCC) progression are still unknown. The present study is aimed to investigate the detailed functions and the mechanism of TP73-AS1 in regulation of HCC cell proliferation. TP73-AS1 expression in HCC tissues and cell lines was determined using real-time PCR assays; the correlation of TP73-AS1 expression with clinicopathological features of HCC was analyzed. The functions of TP73-AS1 in regulation of HCC cell proliferation was evaluated using MTT and BrdU assays. The candidate upstream miRNAs of HMGB1 were screened using miRcode, miRWalk, miRanda and Target scan, verified using real-time PCR assays. The interaction between TP73-AS1 and miR-200a was confirmed using Luciferase report gene assays. The proten levels of HMGB1 signaling-related factors in response to co-processing TP73-AS1 knockdown and miR-200a inhibition were determined using Western blot assays and ELISA. Further, miR-200a, HMGB1 mRNA and RAGE mRNA and their correlations in HCC tissues were determined. TP73-AS1 was upregulated in HCC tissues and cell lines. High TP73-AS1 expression was correlated with worse clinicopathological features, poorer prognosis and shorter survival. Knockdown of TP73-AS1 inhibited the HCC proliferation and the expression levels of HMGB1, RAGE and NF-κB in HCC cells. By using online tools, we screened out several candidate upstream miRNAs of HMGB1, among which miR-200a overexpression inhibited HMGB1 mRNA expression the most significantly. By using luciferase assays, we confirmed that miR-200a could directly bind to TP73-AS1 and the 3’UTR of HMGB1; TP73-AS1 competed with HMGB1 for miR-200a binding. MiR-200a inhibition could up-regulate HMGB1, RAGE, NF-κB expression as well as NF-κB regulated cytokines levels, which could be partially restored by si-TP73-AS1. In HCC tissues, miR-200a was down-regulated while HMGB1 and RAGE were up-regulated; TP73-AS1 was inversely correlated with miR-200a, while positively correlated with HMGB1 and RAGE, respectively. Our data indicated that TP73-AS1 might be an oncogenic lncRNA that promoted proliferation of HCC and could be regarded as a therapeutic target in human HCC.

/pdf/the-long-non-coding-rna-tp73-as1-modulates-hcc-cell-2v661xd87n.pdf

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation.

Hepatocellular Carcinoma (HCC) is one of the most predominant malignancies with high fatality rate. This deadly cancer is rising at an alarming rate because it is quite resistant to radio- and chemotherapy. Different epigenetic mechanisms such as histone modifications, DNA methylation, chromatin remodeling, and expression of noncoding RNAs drive the cell proliferation, invasion, metastasis, initiation, progression, and development of HCC. These epigenetic alterations because of potential reversibility open way towards the development of biomarkers and therapeutics. The contribution of these epigenetic changes to HCC development has not been thoroughly explored yet. Further research on HCC epigenetics is necessary to better understand novel molecular-targeted HCC treatment and prevention. This review highlights latest research progress and current updates regarding epigenetics of HCC, biomarker discovery, and future preventive and therapeutic strategies to combat the increasing risk of HCC.

/pdf/new-insights-into-the-epigenetics-of-hepatocellular-1u4qivxy7h.pdf

New Insights into the Epigenetics of Hepatocellular Carcinoma

Long noncoding RNAs (lncRNAs) have been proved to play important roles in the tumorigenesis and development of human hepatocellular carcinoma (HCC). The aim of our study is to investigate the expression and function of BRAF-activated noncoding RNA (BANCR) in HCC. BANCR expression was detected in HCC tissues and cell lines by using quantitative real-time PCR (qRT-PCR). Association between BANCR levels and clinicopathological factors and patient prognosis was also analyzed. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometry, and transwell invasion and migration assays were used to investigate the role of BANCR in the regulation of biological behaviors of HCC cells. BANCR expression was remarkably increased in HCC tissues compared with adjacent noncancerous tissues (P < 0.001). BANCR expression in four HCC cell lines was also significantly upregulated (P < 0.05). Clinicopathologic analysis revealed that high BANCR expression correlated with high tumor grade, large tumor size, venous infiltration, advanced tumor, node, and metastasis (TNM) stage, and shorter overall survival. Multivariate regression analysis identified BANCR overexpression as an independent unfavorable prognostic factor (relative risk [RR] 4.245; P = 0.015) in HCC patients. Moreover, BANCR downregulation in Hep3B cells impaired cell proliferation, promoted cell apoptosis, reduced cell invasion and migration, led to downregulated vimentin, and upregulated E-cadherin protein levels. These findings suggested that BANCR may contribute to HCC initiation and progression and would be used as not only a novel prognostic marker but also a potential therapeutic target for this disease.

/pdf/increased-expression-of-lncrna-bancr-and-its-prognostic-1mpxs736h3.pdf

Increased expression of LncRNA BANCR and its prognostic significance in human hepatocellular carcinoma.

Gastric cancer (GC) is a very common malignancy with a poor prognosis, and its occurrence and development are closely related to epigenetic modifications. Methylation of DNA before or during gastric cancer is an interesting research topic. This article reviews the studies on DNA methylation related to the cause, diagnosis, treatment, and prognosis of gastric cancer and aims to find cancer biomarkers to solve major human health problems.

/pdf/dna-methylation-an-important-biomarker-and-therapeutic-2w9sh62p.pdf

DNA Methylation: An Important Biomarker and Therapeutic Target for Gastric Cancer

Partial splenic embolization combined with endoscopic therapies and vasoconstrictive drugs reduces rebleeding in cirrhosis patients with acute variceal bleeding and hypersplenism: a multicenter randomized controlled trial

We presented a rare case of gastric adenocarcinoma with enteroblastic differentiation with pancreatic hepatoid adenocarcinoma metastasis. Tumors in the primitive site of the stomach and metastatic site in the pancreas demonstrated different morphological characteristics. Endoscopic-assisted tissue acquisition played a pivotal role in presurgical assessment, but may still trap in the pitfall in such a rare and obfuscated pathological case. This case highlights the significance of being acquainted with the diversity of pancreatic tumors, which brings challenges to clinical differential diagnosis in practice.

A rare case of gastric adenocarcinoma with enteroblastic differentiation presenting as pancreatic hepatoid adenocarcinoma metastases

Expression of Concern to: World J Surg Oncol https://doi.org/10.1186/s12957-015-0757-5 The Editor-in-Chief is issuing an editorial expression of concern to alert readers that the following articles published within a very close time frame contain similarities in text and figures to this article [1]. Image si-BANCR in Figs. 3D and 4 in article [2] are very similar to images presented in Fig. 3D as well as the western blot in Fig. 4 in this article. Fig. 3C is very similar to Fig. 3C in retracted article [3]. Image si-NC in Fig. 3E in article [4] is very similar to Fig. 3D of this article. Significant text overlap has been found in articles [5, 6] with this article. The authors have stated that a language editing company submitted a wrong article on their behalf. The matter has been referred to the authors’ institution for further investigation. None of the authors agree to this EEoC.

/pdf/expression-of-concern-to-increased-expression-of-lncrna-1n41iqlr08.pdf

Expression of Concern to: Increased expression of LncRNA BANCR and its prognostic significance in human hepatocellular carcinoma.

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