Emerging molecular mechanisms underlying cancer metastasis: the rising role of the long non-coding RNA GAS5

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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The functional role of oncogenic lncRNA BCAR4 for cancer outcome

Current Pharmaceutical Design ◽

10.2174/1381612827666210604114955 ◽

2021 ◽

Vol 27 ◽

Author(s):

Bei Wang ◽

Wen Xu ◽

Yuxuan Cai ◽

Kai Liu ◽

Jiacheng Wu ◽

...

Keyword(s):

Breast Cancer ◽

Gastric Cancer ◽

Molecular Mechanisms ◽

Clinical Value ◽

Non Coding Rna ◽

Entry Points ◽

Multiple Processes ◽

Cancer Outcome ◽

Long Non Coding Rna

Background: Long non-coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) is a characterized oncogenic lncRNA in different cancers. This review is dedicated to summarize various molecular mechanisms of BCAR4 and demonstrate that the biological functions exerted by BCAR4 are good entry points for therapy. Methods: The molecular mechanism of BCAR4 acting on tumors is summarized by reviewing PubMed. Results: The expression of lncRNA BCAR4 is abnormally increased in all kinds of tumors, including colorectal cancer, prostate cancer, bladder cancer, gastric cancer, chondrosarcoma, glioma, breast cancer, glioma, gastric cancer, liver cancer, cervical cancer, lung cancer, etc. Besides, BCAR4 mediates multiple processes involved in carcinogenesis, including proliferation, invasion, anti-apoptosis, migration. Conclusion: BCAR4 may show great clinical value in this direction as a therapeutic cancer target.

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The Role of Tumor-related LncRNA PART1 in cancer

Current Pharmaceutical Design ◽

10.2174/1381612827666210705161955 ◽

2021 ◽

Vol 27 ◽

Author(s):

Jinlan Chen ◽

Enqing Meng ◽

Yexiang Lin ◽

Yujie Shen ◽

Chengyu Hu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Malignant Tumors ◽

Migration And Invasion ◽

Signal Pathways ◽

Toll Like Receptor ◽

Non Coding Rna ◽

Regulated Expression ◽

The One ◽

Long Non Coding Rna

Background: As we all know, long non-coding RNA (lncRNA) affects tumor progression, which has caused a great upsurge in recent years. It can also affect the growth, migration, and invasion of tumors. When we refer to the abnormal expression of lncRNA, we will find it associated with malignant tumors. In addition, lncRNA has been proved to be a key targeted gene for the treatment of some diseases. PART1, a member of lncRNA, has been reported as a regulator in the process of tumor occurrence and development. This study aims to reveal the biological functions, specific mechanisms, and clinical significance of PART1 in various tumor cells. Methods: Through the careful search of PUBMED, the mechanisms of the effect of PART1 on tumorigenesis and development are summarized. Results: On the one hand, the up-regulated expression of PART1 plays a tumor-promoting role in tumors, including lung cancer, prostate cancer, bladder cancer and so on. On the other hand, PART1 is down-regulated in gastric cancer, glioma and other tumors to play a tumor inhibitory role. In addition, PART1 regulates tumor growth mainly by targeting microRNA such as miR-635, directly regulating the expression of proteins such as FUS/EZH2, affecting signal pathways such as the Toll-like receptor pathway, or regulating immune cells. Conclusion: PART1 is closely related to tumors by regulating a variety of molecular mechanisms. In addition, PART1 can be used as a clinical marker for the early diagnosis of tumors and plays an important role in tumor-targeted therapy.

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The role of long non-coding RNA ANRIL in chemosensitivity in osteosarcoma and clinical outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e22515 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e22515-e22515

Author(s):

Asmaa Ferdjallah ◽

Adam M Lee ◽

Elise Moore ◽

Aritro Nath ◽

R. Stephanie Huang

Keyword(s):

Cancer Metastasis ◽

Drug Regimen ◽

Outcome Analysis ◽

Osteosarcoma Cell ◽

Non Coding Rna ◽

Cellular Sensitivity ◽

Using Data ◽

Sirna Knockdown ◽

Long Non Coding Rna

e22515 Background: Osteosarcoma is a skeletal malignancy affecting children, adolescents, and young adults. Surgical resection and chemotherapy are the mainstay of therapy with a three-drug regimen - cisplatin, doxorubicin, and methotrexate. However, prognosis remains poor mainly due to chemo-resistance and/or metastases. Emerging evidence has shown that long non-coding RNAs (lncRNAs) are implicated in drug sensitivity and cancer metastasis. Our lab has recently identified strong significant association between cellular sensitivity to cisplatin and doxorubicin and expression of a lncRNA ANRIL in a collection of osteosarcoma cell lines. Methods: SiRNA knockdown experiments were carried out in an osteosarcoma cell line, SAOS2. Cells were exposed to multiple concentrations of cisplatin or doxorubicin. Cellular sensitivity to these two drugs was quantified after siRNA experiment with siRNA targeting ANRIL and scramble control at 24, 48 and 72h. Clinical outcome analysis was performed using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Results: We successfully knocked down ANRIL expression in SAOS2 cells with 88.5% efficiency. A significant decreased rate of proliferation was detected for cisplatin (7 uM, 72h) in knockdown cells (16.5% +/- 4.1) compared to scramble control (26.4% +/- 0.8). The cisplatin IC50 was decreased in the siRNA knockdown condition as compared to scramble control at 72h (p = 0.02). For doxorubicin, the IC50 was also significantly decreased in the siRNA knockdown condition as compared to scramble control (p = 0.002 and 0.007 at 24h and 72h, respectively). Survival outcomes, metastases at diagnosis, and percent necrosis (an indicator of treatment response) were evaluated in TARGET osteosarcoma patients (n = 121 and n = 43 for OS, percent necrosis, respectively) with varying degrees of ANRIL expression. Above the median ANRIL expression was associated with a greater number of death (p = 0.004) and higher chances of metastases at diagnosis (p = 0.013). Conclusions: Reducing ANRIL expression led to increased cellular sensitivity to cisplatin and doxorubicin, two key treatment agents for osteosarcoma. Higher ANRIL expression was significantly associated with higher rates of osteosarcoma death and metastases at diagnosis in a clinical cohort of patients. These findings may suggest ANRIL serves as a novel biomarker of cisplatin and doxorubicin sensitivity in osteosarcoma.

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Role of long non-coding RNA H19 in the development of osteoporosis

Molecular Medicine ◽

10.1186/s10020-021-00386-0 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Senxiang Chen ◽

Da Liu ◽

Zimo Zhou ◽

Sen Qin

Keyword(s):

Molecular Mechanisms ◽

The Body ◽

Research Progress ◽

Effective Prevention ◽

Treatment Of Osteoporosis ◽

Non Coding Rna ◽

Metabolic Bone ◽

Different Types ◽

Long Non Coding Rna

Abstract Background Osteoporosis is a widespread and serious metabolic bone disease. At present, revealing the molecular mechanisms of osteoporosis and developing effective prevention and treatment methods are of great significance to health worldwide. LncRNA is a non-coding RNA peptide chain with more than 200 nucleotides. Researchers have identified many lncRNAs implicated in the development of diseases and lncRNA H19 is an example. Results A large amount of evidence supports the fact that long non-coding RNA (lncRNA) genes, such as H19, have multiple, far-reaching effects on various biological functions. It has been found that lncRNA H19 has a role in the regulation of different types of cells in the body including the osteoblasts, osteocytes, and osteoclasts found in bones. Therefore, it can be postulated that lncRNA H19 affects the incidence and development of osteoporosis. Conclusion The prospect of targeting lncRNA H19 in the treatment of osteoporosis is promising because of the effects that lncRNA H19 has on the process of osteogenic differentiation. In this review, we summarize the molecular pathways and mechanisms of lncRNA H19 in the pathogenesis of osteoporosis and summarize the research progress of targeting H19 as a treatment option. Research is emerging that explores more effective treatment possibilities for bone metabolism diseases using molecular targets.

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Expression of long non-coding RNAs ROR and MALAT1 in uterine fibroids

Voprosy ginekologii akušerstva i perinatologii ◽

10.20953/1726-1678-2021-4-17-21 ◽

2021 ◽

Vol 20 (4) ◽

pp. 17-21

Author(s):

S.A. Levakov ◽

◽

G.Ya. Azadova ◽

A.E. Mamedova ◽

Kh.R. Movtaeva ◽

...

Keyword(s):

Molecular Mechanisms ◽

Uterine Fibroids ◽

Reproductive Age ◽

Expression Level ◽

Control Group ◽

Tissue Samples ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Objective. To study the expression level of long non-coding RNAs ROR and MALAT1 in tissue samples of uterine fibroids. Patients and methods. Samples of myomatous nodes and tissues of normal myometrium in 28 women of reproductive age were examined. The analysis of the expression of long non-coding RNAs was carried out using a real-time reverse-transcription polymerase chain reaction (RT-PCR) with specific primers. Results. There was a significant decrease in the expression level of long non-coding RNA ROR and an increase in the MALAT1 expression in tissue samples of uterine fibroids relative to the control group. Conclusion. The results obtained demonstrate a possible role of long non-coding RNAs in the development of uterine fibroids and correlate with the data which we obtained for patients with endometriosis. Detecting the expression level of long non-coding RNAs can improve the existing methods for diagnosing this disease. However, further research is required to determine the clinical significance of MALAT1 and ROR, and the molecular mechanisms underlying the action of these RNAs in uterine fibroid cells. Key words: long non-coding RNAs, uterine fibroids, myomectomy, lncROR, MALAT1

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Long Non-coding RNA: An Emerging Contributor and Potential Therapeutic Target in Renal Fibrosis

Frontiers in Genetics ◽

10.3389/fgene.2021.682904 ◽

2021 ◽

Vol 12 ◽

Author(s):

Weiping Xia ◽

Yao He ◽

Yu Gan ◽

Bo Zhang ◽

Guoyu Dai ◽

...

Keyword(s):

Renal Fibrosis ◽

Molecular Mechanisms ◽

Pathological Process ◽

Major Type ◽

Future Research ◽

Non Coding Rna ◽

Future Research Directions ◽

Non Coding Rnas ◽

Long Non Coding Rna

Renal fibrosis (RF) is a pathological process that culminates in terminal renal failure in chronic kidney disease (CKD). Fibrosis contributes to progressive and irreversible decline in renal function. However, the molecular mechanisms involved in RF are complex and remain poorly understood. Long non-coding RNAs (lncRNAs) are a major type of non-coding RNAs, which significantly affect various disease processes, cellular homeostasis, and development through multiple mechanisms. Recent investigations have implicated aberrantly expressed lncRNA in RF development and progression, suggesting that lncRNAs play a crucial role in determining the clinical manifestation of RF. In this review, we comprehensively evaluated the recently published articles on lncRNAs in RF, discussed the potential application of lncRNAs as diagnostic and/or prognostic biomarkers, proposed therapeutic targets for treating RF-associated diseases and subsequent CKD transition, and highlight future research directions in the context of the role of lncRNAs in the development and treatment of RF.

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Long Non-Coding RNA MEG3 in Cellular Stemness

International Journal of Molecular Sciences ◽

10.3390/ijms22105348 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5348

Author(s):

Pei-Fang Hsieh ◽

Cheng-Chia Yu ◽

Pei-Ming Chu ◽

Pei-Ling Hsieh

Keyword(s):

Stem Cells ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Cellular Processes ◽

Lineage Differentiation ◽

Non Coding Rna ◽

Regulatory Functions ◽

Long Non Coding Rna ◽

Large Repertoire

Long non-coding RNAs (lncRNAs) regulate a diverse array of cellular processes at the transcriptional, post-transcriptional, translational, and post-translational levels. Accumulating evidence suggests that lncRNA MEG3 exerts a large repertoire of regulatory functions in cellular stemness. This review focuses on the molecular mechanisms by which lncRNA MEG3 functions as a signal, scaffold, guide, and decoy for multi-lineage differentiation and even cancer progression. The role of MEG3 in various types of stem cells and cancer stem cells is discussed. Here, we provide an overview of the functional versatility of lncRNA MEG3 in modulating pluripotency, differentiation, and cancer stemness.

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LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression

Open Life Sciences ◽

10.1515/biol-2021-0002 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1-13

Author(s):

Weiwei Liu ◽

Dongmei Yao ◽

Bo Huang

Keyword(s):

Cervical Cancer ◽

Cancer Progression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Nude Mouse Model ◽

Western Blot Assay ◽

Non Coding Rna ◽

Long Non Coding Rna

Abstract Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 in vivo. PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth in vivo. PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.

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Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis

Cell Death and Disease ◽

10.1038/s41419-020-03346-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Min Lu ◽

Xinglei Qin ◽

Yajun Zhou ◽

Gang Li ◽

Zhaoyang Liu ◽

...

Keyword(s):

Acquired Resistance ◽

Transcriptional Regulators ◽

First Line ◽

Protein Coding ◽

Gemcitabine Resistance ◽

Non Coding Rna ◽

Sphere Formation ◽

Long Non Coding Rna ◽

Line Chemotherapy

AbstractGemcitabine is the first-line chemotherapy drug for cholangiocarcinoma (CCA), but acquired resistance has been frequently observed in CCA patients. To search for potential long noncoding RNAs (lncRNAs) involved in gemcitabine resistance, two gemcitabine resistant CCA cell lines were established and dysregulated lncRNAs were identified by lncRNA microarray. Long intergenic non-protein coding RNA 665 (LINC00665) were found to rank the top 10 upregulated lncRNAs in our study, and high LINC00665 expression was closely associated with poor prognosis and chemoresistance of CCA patients. Silencing LINC00665 in gemcitabine resistant CCA cells impaired gemcitabine tolerance, while enforced LINC00665 expression increased gemcitabine resistance of sensitive CCA cells. The gemcitabine resistant CCA cells showed increased EMT and stemness properties, and silencing LINC00665 suppressed sphere formation, migration, invasion and expression of EMT and stemness markers. In addition, Wnt/β-Catenin signaling was activated in gemcitabine resistant CCA cells, but LINC00665 knockdown suppressed Wnt/β-Catenin activation. B-cell CLL/lymphoma 9-like (BCL9L), the nucleus transcriptional regulators of Wnt/β-Catenin signaling, plays a key role in the nucleus translocation of β-Catenin and promotes β-Catenin-dependent transcription. In our study, we found that LINC00665 regulated BCL9L expression by acting as a molecular sponge for miR-424-5p. Moreover, silencing BCL9L or miR-424-5p overexpression suppressed gemcitabine resistance, EMT, stemness and Wnt/β-Catenin activation in resistant CCA cells. In conclusion, our results disclosed the important role of LINC00665 in gemcitabine resistance of CCA cells, and provided a new biomarker or therapeutic target for CCA treament.

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