1.Matrix stiffening related lncRNA SNHG8 regulates chemosensitivity of ovarian cancer.
Zina CHENG ; Xiaolu MA ; Quanyou ZHANG ; Weiyi CHEN
Journal of Biomedical Engineering 2023;40(1):87-94
Extracellular matrix (ECM) has been implicated in tumor progress and chemosensitivity. Ovarian cancer brings a great threat to the health of women with a significant feature of high mortality and poor prognosis. However, the potential significance of matrix stiffness in the pattern of long non-coding RNAs (lncRNAs) expression and ovarian cancer drug sensitivity is still largely unkown. Here, based on RNA-seq data of ovarian cancer cell cultured on substrates with different stiffness, we found that a great amount of lncRNAs were upregulated in stiff group, whereas SNHG8 was significantly downregulated, which was further verified in ovarian cancer cells cultured on polydimethylsiloxane (PDMS) hydrogel. Knockdown of SNHG8 led to an impaired efficiency of homologous repair, and decreased cellular sensitivity to both etoposide and cisplatin. Meanwhile, the results of the GEPIA analysis indicated that the expression of SNHG8 was significantly decreased in ovarian cancer tissues, which was negatively correlated with the overall survival of patients with ovarian cancer. In conclusion, matrix stiffening related lncRNA SNHG8 is closely related to chemosensitivity and prognosis of ovarian cancer, which might be a novel molecular marker for chemotherapy drug instruction and prognosis prediction.
Female
;
Humans
;
Cisplatin/pharmacology*
;
Elasticity/physiology*
;
Etoposide
;
Extracellular Matrix/physiology*
;
Ovarian Neoplasms/metabolism*
;
RNA, Long Noncoding/metabolism*
2.Roles of PTBP1 in alternative splicing, glycolysis, and oncogensis.
Wei ZHU ; Bo-Lun ZHOU ; Li-Juan RONG ; Li YE ; Hong-Juan XU ; Yao ZHOU ; Xue-Jun YAN ; Wei-Dong LIU ; Bin ZHU ; Lei WANG ; Xing-Jun JIANG ; Cai-Ping REN
Journal of Zhejiang University. Science. B 2020;21(2):122-136
Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.
Alternative Splicing
;
Carcinogenesis
;
Glycolysis
;
Heterogeneous-Nuclear Ribonucleoproteins/physiology*
;
Humans
;
MicroRNAs/physiology*
;
Neoplasms/pathology*
;
Polypyrimidine Tract-Binding Protein/physiology*
;
RNA, Long Noncoding/physiology*
3.Role of LINC00152 in non-small cell lung cancer.
Journal of Zhejiang University. Science. B 2020;21(3):179-191
Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. The pathogenesis of NSCLC involves complex gene networks that include different types of non-coding RNAs, such as long non-coding RNAs (lncRNAs). The role of lncRNAs in NSCLC is gaining an increasing interest as their function is being explored in various human cancers. Recently, a new oncogenic lncRNA, LINC00152 (cytoskeleton regulator RNA (CYTOR)), has been identified in different tumor types. In NSCLC, the high expression of LINC00152 in tumor tissue and peripheral blood samples has been shown to be associated with worse prognoses of NSCLC patients. Overexpression of LINC00152 has been confirmed to promote the proliferation, invasion, and migration of NSCLC cells in vitro, as well as increase tumor growth in vivo. This review discusses the role of LINC00152 in NSCLC.
Apoptosis
;
Biomarkers, Tumor/blood*
;
Carcinoma, Non-Small-Cell Lung/radiotherapy*
;
Cell Cycle Checkpoints
;
Computational Biology
;
Epithelial-Mesenchymal Transition
;
Humans
;
Lung Neoplasms/radiotherapy*
;
Prognosis
;
RNA, Long Noncoding/physiology*
;
Radiation Tolerance
4.Roles of miRNA and lncRNA in triple-negative breast cancer.
Juan XU ; Kang-Jing WU ; Qiao-Jun JIA ; Xian-Feng DING
Journal of Zhejiang University. Science. B 2020;21(9):673-689
Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancer without effective targeted therapies, which makes its pathogenesis an important target for research. A growing number of studies have shown that non-coding RNA (ncRNA), including microRNA (miRNA) and long non-coding RNA (lncRNA), plays a significant role in tumorigenesis. This review summarizes the roles of miRNA and lncRNA in the progression, diagnosis, and neoadjuvant chemotherapy of TNBC. Aberrantly expressed miRNA and lncRNA are listed according to their roles. Further, it describes the multiple mechanisms that lncRNA shows for regulating gene expression in the nucleus and cytoplasm, and more importantly, describes lncRNA-regulated TNBC progression through complete combining with miRNA at the post-transcriptional level. Focusing on miRNA and lncRNA associated with TNBC can provide new insights for early diagnosis and treatment-they can be targeted in the future as a novel anticancer target of TNBC.
Female
;
Gene Expression Regulation, Neoplastic
;
Humans
;
MicroRNAs/physiology*
;
Neoadjuvant Therapy
;
RNA, Long Noncoding/physiology*
;
Triple Negative Breast Neoplasms/pathology*
5.Long noncoding RNA LINC00520 prevents the progression of cutaneous squamous cell carcinoma through the inactivation of the PI3K/Akt signaling pathway by downregulating EGFR.
Chinese Medical Journal 2019;132(4):454-465
BACKGROUND:
Long noncoding RNAs (lncRNAs) play pivotal roles in various malignant tumors. Epidermal growth factor receptor (EGFR) signaling is associated with the pathogenesis of cutaneous squamous cell carcinoma (cSCC). This study aimed to explore the role of LINC00520 in the development of cSCC via EGFR and phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) signaling pathways.
METHODS:
A microarray analysis was applied to screen differentially expressed lncRNAs in cSCC samples. The A431 cSCC cell line was transfected and assigned different groups. The expression patterns of LINC00520, EGFR, and intermediates in the PI3K/Akt pathway were characterized using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis. Cell proliferation, migration, and invasion were detected using the MTT assay, scratch test, and Transwell assay, respectively. Cell-based experiments and a tumorigenicity assay were conducted to assess the effect of LINC00520 on cSCC progression. This study was ended in September 2017. Comparisons between two groups were analyzed with t-test and comparisons among multiple groups were analyzed using one-way analysis of variance. The nonparametric Wilcoxon rank sum test was used to analyze skewed data. The enumerated data were analyzed using the chi-square test or Fisher exact test.
RESULTS:
Data from chip GSE66359 revealed depletion of LINC00520 in cSCC. Cells transfected with LINC00520 vector and LINC00520 vector + si-EGFR showed elevated LINC00520 level but decreased levels of the EGFR, PI3K, AKT, VEGF, MMP-2 and MMP-9 mRNAs and proteins, and inhibition of the growth, migration and adhesion of cSCC cells, while the si-LINC00520 group showed opposite trends (all P < 0.05). Compared with the LINC00520 vector group, the LINC00520 vector + si-EGFR group showed decreased levels of the EGFR, PI3K, AKT, VEGF, MMP-2 and MMP-9 mRNAs and proteins, and inhibition of the growth, migration and adhesion of cSCC cells, while the LINC00520 vector + EGFR vector group showed opposite results (all P < 0.05).
CONCLUSION
Based on our results, LINC00520-targeted EGFR inhibition might result in the inactivation of the PI3K/Akt pathway, thus inhibiting cSCC development.
Animals
;
Carcinoma, Squamous Cell
;
pathology
;
prevention & control
;
Cell Line, Tumor
;
Cell Movement
;
Cell Proliferation
;
Disease Progression
;
ErbB Receptors
;
antagonists & inhibitors
;
Female
;
Humans
;
Lymphatic Metastasis
;
Mice
;
Neoplasm Invasiveness
;
Phosphatidylinositol 3-Kinases
;
physiology
;
Proto-Oncogene Proteins c-akt
;
physiology
;
RNA, Long Noncoding
;
physiology
;
Signal Transduction
;
physiology
;
Skin Neoplasms
;
pathology
;
prevention & control
6.Exosomal long non-coding RNAs: biological properties and therapeutic potential in cancer treatment.
Jie LUO ; Yan XIONG ; Pei-Fen FU ; En-Chun LI ; Lei QU ; Xiao FAN ; Zhi-Jian CAI ; Ai-Fu LIN
Journal of Zhejiang University. Science. B 2019;20(6):488-495
Exosomes and long non-coding RNAs (lncRNAs) are emerging as important elements contributing to a more comprehensive understanding of cancer development and progression. The discovery of lncRNAs in exosomes further indicates their bona fide biological functional roles in cancer development and drug resistance. In this review, we describe the biogenesis of exosomes and summarize the function of exosomal lncRNAs in the field of cancer research. These findings strikingly advance current knowledge of exosomal lncRNAs and suggest that they may be promising diagnostic biomarkers and therapeutic targets for cancer.
Exosomes
;
physiology
;
Humans
;
Neoplasms
;
diagnosis
;
genetics
;
therapy
;
RNA, Long Noncoding
;
physiology
7.Genomic data mining for functional annotation of human long noncoding RNAs.
Brian L GUDENAS ; Jun WANG ; Shu-Zhen KUANG ; An-Qi WEI ; Steven B COGILL ; Liang-Jiang WANG
Journal of Zhejiang University. Science. B 2019;20(6):476-487
Life may have begun in an RNA world, which is supported by increasing evidence of the vital role that RNAs perform in biological systems. In the human genome, most genes actually do not encode proteins; they are noncoding RNA genes. The largest class of noncoding genes is known as long noncoding RNAs (lncRNAs), which are transcripts greater in length than 200 nucleotides, but with no protein-coding capacity. While some lncRNAs have been demonstrated to be key regulators of gene expression and 3D genome organization, most lncRNAs are still uncharacterized. We thus propose several data mining and machine learning approaches for the functional annotation of human lncRNAs by leveraging the vast amount of data from genetic and genomic studies. Recent results from our studies and those of other groups indicate that genomic data mining can give insights into lncRNA functions and provide valuable information for experimental studies of candidate lncRNAs associated with human disease.
Autism Spectrum Disorder
;
genetics
;
Data Mining
;
Genomics
;
Humans
;
Machine Learning
;
RNA, Long Noncoding
;
analysis
;
physiology
;
Support Vector Machine
8.Biological Function and Mechanism of Long Noncoding RNAs Nuclear-Enriched Abundant Transcript 1 in Development of Cervical Cancer.
Hui-Ling WANG ; Shun-Yu HOU ; Hai-Bo LI ; Jian-Ping QIU ; Le BO ; Cai-Ping MAO
Chinese Medical Journal 2018;131(17):2063-2070
Background:
Accumulating documents have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis. As an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1) has been identified to be involved in the progression of many types of cancers. However, the biological function of NEAT1 in cervical cancer is not fully investigated. The aim of this study was to disclose the specific biological function of lncRNA NEAT1 in cervical cancer progression.
Methods:
Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to identify the expression of lncRNA NEAT1 in the cervical cancer tissues and cell lines. All cervical cancer samples used in this study were collected from the Affiliated Suzhou Hospital of Nanjing Medical University between September 2012 and September 2017. The correlation between NEAT1 expression and the overall survival rate of cervical cancer patients was analyzed by Kaplan-Meier analysis. The effects of NEAT1 knockdown or overexpression on cell proliferation were tested by performing MTT assays and colony formation assays. Transwell assays were conducted to detect the migratory ability of cervical cancer cells, in which NEAT1 was silenced or overexpressed. Western blotting was utilized to validate whether NEAT1 promotes cervical cancer progression through activating PI3K-Akt signaling pathway.
Results:
High expression of NEAT1 predicted poor prognosis of cervical cancer patients (χ = 0.735, P = 0.005). Knockdown of NEAT1 decreased the number of colonies in CaSki cell from 136.667 ± 13.503 to 71.667 ± 7.506 (t = -18.76, P = 0.003) and decreased the number of colonies in HeLa cell from 128.667 ± 13.317 to 65.667 ± 7.024 (t = -5.54, P = 0.031). However, overexpression of NEAT1 increased the number of colonies in SiHa cell from 84.667 ± 12.014 to 150.667 ± 18.037 (t = 7.27, P = 0.018). Knockdown of NEAT1 decreased the migratory number of CaSki cell from 100.333 ± 9.866 to 58.333 ± 5.859 (t = -8.08, P = 0.015) and reduced the migratory number in HeLa cell from 123.667 ± 12.097 to 67.667 ± 7.095 (t = -6.03, P = 0.026). Overexpression of NEAT1 increased the migratory number of SiHa cell from 127.333 ± 16.042 to 231.333 ± 31.786 (t = 4.92, P = 0.039).
Conclusion
NEAT1 may exert oncogenic function in cervical cancer and serve as a novel therapeutic target for cervical cancer.
Cell Line, Tumor
;
Cell Proliferation
;
Female
;
HeLa Cells
;
Humans
;
Middle Aged
;
Phosphatidylinositol 3-Kinases
;
physiology
;
RNA, Long Noncoding
;
physiology
;
Uterine Cervical Neoplasms
;
genetics
9.Research progress of long chain non-coding RNA H19 in anoxic environment mechanism.
Xinrui YUE ; Rong WANG ; Wenbin LI ; Chang WANG ; Hui LU ; Juanhong ZHANG
Journal of Central South University(Medical Sciences) 2018;43(10):1151-1158
LncRNA H19 encoded by the H19 imprinting gene plays an important regulatory role in the cell. Recently study has found that in hypoxic cells, the expression of H19 gene changes, and the transcription factors and protein involved in the expression change accordingly. Through the involvement of specific protein 1 (SP1), hypoxia-inducible factor-1α (HIF-1α) binds directly to the H19 promoter and induces the up-regulation of H19 expression under hypoxic conditions. The tumor suppressor protein p53 may also mediate the expression of the H19 gene, in part by interfering with HIF-la activity under hypoxia stress. The miR675-5p encoded by exon 1 of H19 promotes hypoxia response by driving the nuclear accumulation of HIF-1α and reducing the expression of VHL gene, which is a physiological HIF-1α inhibitor. In addition, under the condition of hypoxia, the expression of transporter on cell membrane changes, and the transition of the intracellular glucose metabolism pathway from aerobic oxidation to anaerobic glycolysis is also involved in the involvement of H19. Therefore, H19 may be a key gene that maintains intracellular balance under hypoxic conditions and drives adaptive cell survival under conditions of hypoxia stress.
Cell Hypoxia
;
genetics
;
Genes, Tumor Suppressor
;
physiology
;
Humans
;
Hypoxia-Inducible Factor 1, alpha Subunit
;
genetics
;
RNA, Long Noncoding
;
Up-Regulation
;
physiology
;
Von Hippel-Lindau Tumor Suppressor Protein
;
genetics
10.Research progress of long noncoding RNA in regulating adipogenesis.
Haoneng TANG ; Yaru CHEN ; Houde ZHOU
Journal of Central South University(Medical Sciences) 2018;43(8):912-919
Long noncoding RNA (lncRNA) is once thought to be the genome transcriptional "noise". However, it has received considerable attention in the past few years and is emerging as potentially important player in biological regulation. Recent studies have revealed that increasing number of lncRNA plays pivotal roles in regulating the gene expression which involves in the development of the human disease. Functions of lncRNA include 3 types of interaction: RNA-RNA, RNA-DNA, and RNA-protein, which may participate in gene expression regulation through epigenetic modifications, transcriptional regulation, post-transcriptional regulation, acting as biological media. Due to the prevalence of obesity and related diseases, some attempts have been done to explore the pathogenesis of obesity from the field of noncoding RNA. Several lncRNAs have been identified to be involved in the regulation of the adipogenesis (white adipose tissue and brown adipose tissue) and energy metabolism. In this review, we summarized recent advances of lncRNAs to provide a new sight for the mechanism of obesity.
Adipogenesis
;
genetics
;
Epigenesis, Genetic
;
Gene Expression Regulation
;
Humans
;
RNA, Long Noncoding
;
physiology
;
RNA, Untranslated

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