Dysfunctional Mechanism of Liver Cancer Mediated by Transcription Factor and Non-coding RNA

Background:There have been numerous experiments and studies on liver cancer by biomedical scientists, while no comprehensive and systematic exploration has yet been conducted. Therefore, this study aimed to systematically dissect the transcriptional and non-coding RNAmediated mechanisms of liver cancer dysfunction.Method:At first, we collected 974 liver cancer associated genes from the Online Mendelian Inheritance in Man (OMIM). Afterwards, their interactors were recruited from STRING database so as to identify 18 co-expression modules in liver cancer patient expression profile. Crosstalk analysis showed the interactive relationship between these modules. In addition, core drivers for modules were identified, including 111 transcription factors (STAT3, JUN and NFKB1, etc.) and 1492 ncRNAs (FENDRR and miR-340-5p, etc.).Results:In view of the results of enrichment, we found that these core drivers were significantly involved in Notch signaling, Wnt / β-catenin pathways, cell proliferation, apoptosis-related functions and pathways, suggesting they can affect the development of liver cancer. Furthermore, a global effect on bio-network associated with liver cancer has been integrated from the ncRNA and TF pivot network, module crosstalk network, module-function/pathways network. It involves various development and progression of cancer.Conclusion:Overall, our analysis further suggests that comprehensive network analysis will help us to not only understand in depth the molecular mechanisms, but also reveal the influence of related gene dysfunctional modules on the occurrence and progression of liver cancer. It provides a valuable reference for the design of liver cancer diagnosis and treatment.

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Long non-coding RNA HULC affects the proliferation, apoptosis, migration, and invasion of mesenchymal stem cells

Experimental Biology and Medicine ◽

10.1177/1535370218804781 ◽

2018 ◽

Vol 243 (13) ◽

pp. 1074-1082 ◽

Cited By ~ 4

Author(s):

Xiujun Li ◽

Jiali Wang ◽

Yuchen Pan ◽

Yujun Xu ◽

Dan Liu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Cancer ◽

Clinical Application ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Therapeutic Effects ◽

Non Coding Rna ◽

And Function ◽

Long Non Coding Rna

Further studies on the molecular mechanisms of mesenchymal stem cells in the maintenance of growth and function are essential for their clinical application. Growing evidence has shown that long non-coding RNAs (lncRNAs) play an important role in the regulation of mesenchymal stem cells. Recently, it is reported that highly upregulated in liver cancer (HULC), with another lncRNA MALAT-1, accelerated liver cancer stem cell growth. The regulating role of MALAT-1 in mesenchymal stem cells has been investigated. However, the effects of HULC on the mesenchymal stem cells are unknown. In this study, we overexpressed HULC in mesenchymal stem cells derived from umbilical cord and analyzed the cell phenotypes, proliferation, apoptosis, migration, invasion and differentiation of mesenchymal stem cells. We found that overexpression of HULC significantly promotes cell proliferation through promoting cell division and inhibits cell apoptosis. HULC-overexpressed mesenchymal stem cells migrate and invade faster than control mesenchymal stem cells. HULC has no effect on phenotypes and differentiation of mesenchymal stem cells. Furthermore, we found that the expression of HULC in mesenchymal stem cells could be reduced by several inflammatory factors, including TNF-α, TGF-β1, and R848. Taken together, our data demonstrated that HULC has a vital role in the growth and function maintenance of mesenchymal stem cells without affecting differentiation. Impact statement Exploring the molecular mechanisms of growth and function in MSCs is the key to improve their clinical therapeutic effects. Currently, more and more evidence show that the long non-coding RNA (lncRNA) plays an important role in the growth, stemness and function of MSCs.Both HULC and MALAT1 are the earliest discovered LNCRNAs, which are closely related to tumor growth. All of them can promote the growth of liver cancer stem cells. Previously, we have studied the effects of MALAT1 on the growth and function of MSCs. In this study, we focused on the effects of HULC on MSCs. We elucidated the effects of HULC on the growth and differentiation of MSCs, and explored the relationship between inflammatory stimuli and HULC expression in MSCs. Our findings provide a new molecular target for the growth and clinical application of MSCs.

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Anti-Hepatocellular Carcinoma Effect and Molecular Mechanism of the Estrogen Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.763539 ◽

2022 ◽

Vol 11 ◽

Author(s):

Yusheng Guo ◽

Guohui Wu ◽

Junrong Yi ◽

Qin Yang ◽

Wengong Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Treatment Strategies ◽

Estrogen Signaling ◽

Regulatory Pathways ◽

Non Coding Rna ◽

Incidence And Mortality ◽

Complex Functions

There are significant gender differences in the incidence and mortality of hepatocellular carcinoma (HCC). Compared with men, the incidence and mortality of HCC in women are relatively low. The estrogen signaling pathway, composed of estrogen and estrogen receptors, has been postulated to have a protective effect on the occurrence and development of HCC. There have been multiple studies that have supported anti-HCC effects of the estrogen signaling pathways, including direct and indirect pathways such as genomic pathways, rapid transduction pathways, non-coding RNA, tumor microenvironment, estrogen metabolites, and inhibition of hepatitis infection and replication. Based on the evidence of an anti-HCC effect of the estrogen signaling pathway, a number of strategies have been investigated to determine the potential therapeutic effect. These have included estrogen replacement therapy, targeting the estrogen receptor, key molecules, inflammatory mediators, and regulatory pathways of the estrogen signaling pathway. In this review, we have systematically summarized the latest developments in the complex functions and molecular mechanisms of the estrogen signaling pathway in liver cancer. Furthermore, we have highlighted the potential targets of treatment strategies based on the estrogen signaling pathway in the treatment of liver cancer and the principal obstacles currently encountered for future investigation.

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Prevalence and Characteristics of Liver Cancer Patients in Immanuel Hospital Bandung within January 2013 until December 2014 Period

Journal Of Medicine & Health ◽

10.28932/jmh.v1i4.531 ◽

2016 ◽

Vol 1 (4) ◽

Author(s):

Achmad R. Permadi ◽

Hana Ratnawati ◽

Teresa L. Wargasetia

Keyword(s):

Liver Cancer ◽

Cancer Patients ◽

Medical Records ◽

Clinical Symptoms ◽

Data Retrieval ◽

Common Cancer ◽

Key Words Liver Cancer ◽

Liver Cancer Patient ◽

Right Lobe ◽

The Right

Liver cancer is the fifth most common cancer in Indonesia. This research is to find out the prevalence and characteristics of liver cancer patients in Immanuel Hospital Bandung within the January 2013 until December 2014 period based on age, gender, clinical symptoms and predilections. This study was a descriptive verificative research with data retrieval of patients medical records that have been diagnosed with liver cancer that were hospitalized in Immanuel Hospital Bandung within January 2013 until December 2014 period. The study showed that the liver cancer patient prevalence in Immanuel Hospital Bandung within the period of January 2013 until December 2014 was 46 people. Characteristics of liver cancer patients in Immanuel Hospital Bandung within January 2013 until December 2014 period showed that the most liver cancer patients were male, compare with female with ratio 4:1, the most common age group of 56-65 years old, the most common clinical symptoms were abdominal pain with or without reffered pain to the right scapular bone and the most common predilection was right lobe of the liver. Key words: liver cancer, patients' characteristics, prevalence

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Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Cells ◽

10.3390/cells10071715 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1715

Author(s):

Macus Hao-Ran Bao ◽

Carmen Chak-Lui Wong

Keyword(s):

Hepatocellular Carcinoma ◽

Drug Resistance ◽

Liver Cancer ◽

Effective Treatment ◽

Molecular Mechanisms ◽

Hypoxia Inducible Factor ◽

Metabolic Reprogramming ◽

Combination Therapies ◽

Low Oxygen ◽

Treatment Regimens

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

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Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

Journal of Personalized Medicine ◽

10.3390/jpm11060513 ◽

2021 ◽

Vol 11 (6) ◽

pp. 513

Author(s):

Zheng Zhang ◽

Meng Gu ◽

Zhongze Gu ◽

Yan-Ru Lou

Keyword(s):

Molecular Mechanisms ◽

Neurological Diseases ◽

Cellular Processes ◽

Dna And Rna ◽

Chemotherapeutic Response ◽

Non Coding Rna ◽

Response To Chemotherapy ◽

Personalized Oncology ◽

Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

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Small Non-Coding-RNA in Gynecological Malignancies

Cancers ◽

10.3390/cancers13051085 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1085

Author(s):

Shailendra Kumar Dhar Dwivedi ◽

Geeta Rao ◽

Anindya Dey ◽

Priyabrata Mukherjee ◽

Jonathan D. Wren ◽

...

Keyword(s):

Cervical Cancer ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

P Element ◽

Gynecologic Malignancies ◽

Diagnosis And Prognosis ◽

Gynecological Malignancies ◽

Non Coding Rna ◽

Therapeutic Research ◽

Regulatory Functions

Gynecologic malignancies, which include cancers of the cervix, ovary, uterus, vulva, vagina, and fallopian tube, are among the leading causes of female mortality worldwide, with the most prevalent being endometrial, ovarian, and cervical cancer. Gynecologic malignancies are complex, heterogeneous diseases, and despite extensive research efforts, the molecular mechanisms underlying their development and pathology remain largely unclear. Currently, mechanistic and therapeutic research in cancer is largely focused on protein targets that are encoded by about 1% of the human genome. Our current understanding of 99% of the genome, which includes noncoding RNA, is limited. The discovery of tens of thousands of noncoding RNAs (ncRNAs), possessing either structural or regulatory functions, has fundamentally altered our understanding of genetics, physiology, pathophysiology, and disease treatment as they relate to gynecologic malignancies. In recent years, it has become clear that ncRNAs are relatively stable, and can serve as biomarkers for cancer diagnosis and prognosis, as well as guide therapy choices. Here we discuss the role of small non-coding RNAs, i.e., microRNAs (miRs), P-Element induced wimpy testis interacting (PIWI) RNAs (piRNAs), and tRNA-derived small RNAs in gynecological malignancies, specifically focusing on ovarian, endometrial, and cervical cancer.

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Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia

International Journal of Molecular Sciences ◽

10.3390/ijms22052683 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2683

Author(s):

Princess D. Rodriguez ◽

Hana Paculova ◽

Sophie Kogut ◽

Jessica Heath ◽

Hilde Schjerven ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

B Cell ◽

Molecular Mechanisms ◽

Lymphoblastic Leukemia ◽

Transcriptome Profiling ◽

Rna Seq ◽

Protein Coding ◽

Non Coding Rna ◽

Technological Developments ◽

Cell Acute Lymphoblastic Leukemia

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell acute lymphoblastic leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

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Current advances of long non-coding RNA highly upregulated in liver cancer in human tumors

OncoTargets and Therapy ◽

10.2147/ott.s136915 ◽

2017 ◽

Vol Volume 10 ◽

pp. 4711-4717 ◽

Cited By ~ 19

Author(s):

Zhonghua Ma ◽

Hesuyuan Huang ◽

Yetao Xu ◽

Xuezhi He ◽

Jirong Wang ◽

...

Keyword(s):

Liver Cancer ◽

Human Tumors ◽

Non Coding Rna ◽

Long Non Coding Rna

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Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients

Reproduction ◽

10.1530/rep-14-0095 ◽

2014 ◽

Vol 148 (1) ◽

pp. 33-41 ◽

Cited By ~ 48

Author(s):

Fulu Dong ◽

Yuan Zhang ◽

Fei Xia ◽

Yi Yang ◽

Sidong Xiong ◽

...

Keyword(s):

Spontaneous Abortion ◽

Molecular Mechanisms ◽

Target Genes ◽

Expression Profiles ◽

Normal Pregnancy ◽

Recurrent Spontaneous Abortion ◽

Future Research ◽

Rna Molecules ◽

Non Coding Rna ◽

Transcriptional Gene Regulation

MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that involved in post-transcriptional gene regulation. Evidence indicates that miRNAs play essential roles in endometriosis, pre-eclampsia, infertility and other reproductive system diseases. However, whether miRNAs are involved in recurrent spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA expression profiles in six pairs of villus or decidua from RSA patients and normal pregnancy (NP) women using a human miRNA microarray. Some of the chip results were confirmed by RT-qPCR. In the villi of RSA patients, expression of hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly lower, comparing with those of NP control. As well, a total of five miRNAs (hsa-miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were upregulated in the decidua of RSA patients. The target genes of these differentially expressed miRNAs were predicted by miRWalk, and we speculate a network of miRNA regulating RSA by target genes function on adhesion, apoptosis and angiogenesis. Our study may help clarify the molecular mechanisms which are involved in the progression of RSA, and provide a reference for future research.

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