-
Pathology Oncology Research : POR 2021Laryngeal squamous cell carcinoma (LSCC) belongs to head and neck squamous cell carcinoma (HNSCC), with dismal prognosis. Here, this study aims to disclose the role of...
Laryngeal squamous cell carcinoma (LSCC) belongs to head and neck squamous cell carcinoma (HNSCC), with dismal prognosis. Here, this study aims to disclose the role of LINC-PINT in cancer development, which may contribute to improving the clinical outcomes of LSCC treatment. LINC-PINT expression in LSCC tissues and in TU-177 and Hep-2 cells was quantified, and subsequently, the association between LINC-PINT and LSCC malignancies was analyzed. pcDNA3.1-LINC-PINT or pcDNA3.1-EZH2 was introduced into Hep-2 and TU-177 cells. qRT-PCR and Western blot analyses examined the levels of proteins related to the AKT/mTOR pathway and their phosphorylated proteins in Hep-2 and TU-177 cells. The viability as well as migration and invasion abilities of Hep-2 and TU-177 cells were determined. Also, the distribution of LINC-PINT in Hep-2 cells was investigated as well as the interplay between LINC-PINT and EZH2. The downstream genes that might interact with EZH2 were screened. LINC-PINT expression was inhibited in LSCC tissues and in Hep-2 and TU-177 cells, whose downregulation was associated with unsatisfactory prognosis. LINC-PINT overexpression suppressed the proliferative, migratory and invasive capacities of Hep-2 and TU-177 cells. LINC-PINT, mainly expressing in nuclei, could enrich EZH2 to silence ZEB1. In Hep-2 and TU-177 cells, the inhibition of LINC-PINT or overexpression of ZEB1 could enhance cell proliferation, migration and invasion. The phosphorylated levels of proteins related to the AKT/mTOR pathway were declined in cells with LINC-PINT overexpression, and the levels of these phosphorylated proteins were increased in cells with LINC-PINT inhibition. LINC-PINT enriches EZH2 to silence ZEB1 and thus inhibits the proliferative, migratory, and invasive capacities of Hep-2 and TU-177 cells. In addition, LINC-PINT might exert its biological function through the AKT/mTOR pathway.
Topics: Cell Line, Tumor; Cell Movement; Cell Proliferation; Enhancer of Zeste Homolog 2 Protein; Female; Gene Expression Regulation, Neoplastic; Humans; Laryngeal Neoplasms; Male; Middle Aged; Prognosis; Proto-Oncogene Proteins c-akt; RNA, Long Noncoding; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; TOR Serine-Threonine Kinases; Zinc Finger E-box-Binding Homeobox 1
PubMed: 34257531
DOI: 10.3389/pore.2021.584466 -
Cell Biochemistry and Function Dec 2020LncRNA LINC-PINT acts as an important regulator in the development of many cancers. The current study aimed to explore the role of LINC-PINT in the progression of...
LncRNA LINC-PINT acts as an important regulator in the development of many cancers. The current study aimed to explore the role of LINC-PINT in the progression of ovarian cancer (OC). LINC-PINT expression level in different FIGO stages of OC and its adjacent tissues, normal HOSE and OC cell lines (A2780, SKOV3, OVCAR3 and HO-8910) was determined by qRT-PCR. Survival analysis on LINC-PINT and OC patients was conducted by Kaplan-Meier. CCK-8, flow cytometry, wound-healing, Transwell assays and western blot were performed to detect the effects of LINC-PINT on proliferation, apoptosis, migration, invasion and EMT process in OC cells. Target gene of LINC-PINT was predicted by Starbase and verified by dual-luciferase reporter assay. The expression of miR-374a-5p in normal and OC tissues, LINC-PINT- or siLINC-PINT-modified OC cells was determined. Moreover, rescue assay was carried out to confirm whether LINC-PINT contributes to the development of OC cells through targeting miR-374a-5p. Low expression of LINC-PINT was observed in OC tissues and cells, noticeably, LINC-PINT expression was even lower in OC tissues with higher FIGO stage. Increased LINC-PINT expression significantly inhibited cell proliferation, promoted apoptosis and suppressed migration, invasion and EMT process, while silencing of LINC-PINT caused the opposite results. Moreover, LINC-PINT sponged miR-374a-5p and overexpressed miR-374a-5p attenuated the effect of up-regulated LINC-PINT on cell viability, migration, invasion and apoptosis. LINC-PINT acts as a tumour suppressor, as it could inhibit cell proliferation, migration, invasion and EMT process, and promote cell apoptosis through down-regulating miR-374a-5p. SIGNIFICANCE OF THE STUDY: Ovarian cancer (OC), which is a frequently diagnosed tumour in female reproductive organs, has a high incidence rate behind cervical cancer and endometrial cancer. LncRNA LINC-PINT acts as an important regulator in the development of many cancers. The current study aimed to explore the role of LINC-PINT in the progression of ovarian cancer (OC) and found that LINC-PINT inhibited cell proliferation, migration invasion and EMT process of OC cell via regulating miR-374a-5p; it might be a potential target for OC treatment.
Topics: Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Humans; MicroRNAs; Neoplasm Invasiveness; Ovarian Neoplasms; RNA, Long Noncoding; RNA, Neoplasm
PubMed: 32638404
DOI: 10.1002/cbf.3565 -
Biochemical and Biophysical Research... Sep 2020Emerging evidences indicated that long non-coding RNAs (LncRNAs) regulated the pathogenesis of retinoblastoma (RB). However, up until now, the role of LncRNA Linc-PINT...
Emerging evidences indicated that long non-coding RNAs (LncRNAs) regulated the pathogenesis of retinoblastoma (RB). However, up until now, the role of LncRNA Linc-PINT in the regulation of RB progression is still largely unknown. The present study identified LncRNA Linc-PINT as a tumor suppressor to hinder RB development by regulating miR-523-3p/Dickkopf-1 (DKK1) axis. Mechanistically, Linc-PINT was low-expressed, while miR-523-3p was high-expressed in RB cells, compared to the normal retinal epithelial cells (ARPE-19). Further gain- and loss-function experiments verified that both upregulation of Linc-PINT and miR-523-3p downregulation slowed down cell growth, invasion and migration, and promoted cell apoptosis in RB cells, but Linc-PINT ablation and miR-523-3p overexpression promoted malignant phenotypes in RB cells. In addition, the dual-luciferase reporter gene system and RNA pull-down assay validated that Linc-PINT positively regulated DKK1 expressions by sponging miR-523-3p, and Linc-PINT inhibited RB progression by regulating miR-523-3p/DKK1 axis. Functionally, we found that both miR-523-3p overexpression and DKK1 silence abrogated the anti-cancer effects of overexpressed Linc-PINT on RB cells. Finally, Linc-PINT inhibited tumorigenicity of RB cells in xenograft mice models. In general, analysis of the data suggested that Linc-PINT inhibited miR-523-3p to upregulate DKK1, resulting in the inhibition of RB, and we demonstrated that Linc-PINT and miR-523-3p could be utilized as potential diagnostic and therapeutic biomarkers for RB in clinic.
Topics: Animals; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Intercellular Signaling Peptides and Proteins; Male; Mice, Inbred BALB C; RNA, Long Noncoding; Retinal Neoplasms; Retinoblastoma
PubMed: 32828314
DOI: 10.1016/j.bbrc.2020.06.120 -
Archives of Physiology and Biochemistry Apr 2023Type 2 diabetes mellitus (T2DM) is a worldwide disease with rapidly increasing prevalence. This complex disorder caused by interplay between genetic predisposition...
Type 2 diabetes mellitus (T2DM) is a worldwide disease with rapidly increasing prevalence. This complex disorder caused by interplay between genetic predisposition factors, early developmental elements, diet and inactive lifestyle. Several researches have shown impact of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the pathogenesis of this disorder. Several miRNAs such as miR-126, miR-222-3p, miR-182, let-7b-5p, and miR-1-3p have been down-regulated in different biological sources of patients with T2DM. Some other miRNAs including miR-21, miR-30d, miR-148a-3p, miR-146b and miR-486 have the opposite trends. In addition, a number of lncRNAs such as LY86-AS, HCG27_201, VIM-AS1, CTBP1-AS2, CASC2, GAS5, LINC-PINT, and MALAT1 have been altered in the peripheral blood, serum samples or tissues obtained from patients with T2DM. Taken together, both miRNAs and lncRNAs contribute to the development of T2DM and might be applied as markers or therapeutic molecules for this disorder.
Topics: Humans; Diabetes Mellitus, Type 2; RNA, Long Noncoding; MicroRNAs
PubMed: 33155514
DOI: 10.1080/13813455.2020.1843498 -
Cancer Medicine Mar 2020Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) has been reported to participate in various cancers. Here, we investigated the effects of... (Observational Study)
Observational Study
Long intergenic nonprotein coding RNA p53-induced transcript (LINC-PINT) has been reported to participate in various cancers. Here, we investigated the effects of LINC-PINT on lung cancer progression. Firstly, in our study, we implied that LINC-PINT was obviously decreased in NSCLC. Thereafter, in A549 and H1299 cells, LINC-PINT was upregulated via transfecting LV-LINC-PINT. As exhibited, LINC-PINT repressed cell proliferation and cell colony formation of A549 and H1299 cells. Subsequently, flow cytometry evidenced that A549 and H1299 cell apoptosis was obviously triggered and the cell cycle was arrested in G1 phase. Then, migration and transwell invasion experiments were carried out to detect the cell migration and invasion capacity. We found A549 and H1299 cell migration and invasion capacity were restrained by the upregulation of LINC-PINT. Meanwhile, we predicted that miR-543 could function as the target of LINC-PINT and the association was verified. Moreover, we exhibited that miR-543 was remarkably increased in lung cancer, which could be regulated by LINC-PINT negatively. Furthermore, PTEN could act as the downstream target of miR-543 and upregulation of miR-543 repressed PTEN, which was reversed by LV-PINT in A549 and H1299 cells. Finally, xenografts were utilized to confirm the function of LINC-PINT on lung cancer. All these findings concluded that LINC-PINT exerted crucial biological roles in NSCLC through sponging miR-543 and inducing PTEN.
Topics: A549 Cells; Animals; Apoptosis; Biomarkers, Tumor; Cell Movement; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Lung; Lung Neoplasms; Male; Mice; MicroRNAs; Middle Aged; Neoplasm Invasiveness; PTEN Phosphohydrolase; RNA, Long Noncoding; Xenograft Model Antitumor Assays
PubMed: 31981466
DOI: 10.1002/cam4.2822 -
Journal of the American Heart... Aug 2023Background Premature and early menopause are independently associated with greater risk of cardiovascular disease (CVD). However, mechanisms linking age of menopause...
Background Premature and early menopause are independently associated with greater risk of cardiovascular disease (CVD). However, mechanisms linking age of menopause with CVD remain poorly characterized. Methods and Results We measured 71 circulating CVD protein biomarkers in 1565 postmenopausal women enrolled in the FHS (Framingham Heart Study). We examined the association of early menopause with biomarkers and tested whether early menopause modified the association of biomarkers with incident cardiovascular outcomes (heart failure, major CVD, and all-cause death) using multivariable-adjusted linear regression and Cox models, respectively. Among 1565 postmenopausal women included (mean age 62 years), 395 (25%) had a history of early menopause. Of 71 biomarkers examined, we identified 7 biomarkers that were significantly associated with early menopause, of which 5 were higher in women with early menopause including adrenomedullin and resistin, and 2 were higher in women without early menopause including insulin growth factor-1 and CNTN1 (contactin-1) (Benjamini-Hochberg adjusted <0.1 for all). Early menopause also modified the association of specific biomarkers with incident cardiovascular outcomes including adrenomedullin (<0.05). Conclusions Early menopause is associated with circulating levels of CVD protein biomarkers and appears to modify the association between select biomarkers with incident cardiovascular outcomes. Identified biomarkers reflect several distinct biological pathways, including inflammation, adiposity, and neurohormonal regulation. Further investigation of these pathways may provide mechanistic insights into the pathogenesis, prevention, and treatment of early menopause-associated CVD.
Topics: Female; Humans; Middle Aged; Cardiovascular Diseases; Adrenomedullin; Menopause, Premature; Menopause; Biomarkers; Risk Factors
PubMed: 37548169
DOI: 10.1161/JAHA.122.028849 -
Molecular Therapy. Nucleic Acids Dec 2020Long noncoding RNA (lncRNA) long intergenic nonprotein-coding RNA, p53-induced transcript (LINC-PINT) has shown anti-invasive activity in lung and colon cancer cells....
Long noncoding RNA (lncRNA) long intergenic nonprotein-coding RNA, p53-induced transcript (LINC-PINT) has shown anti-invasive activity in lung and colon cancer cells. However, the role of LINC-PINT in thyroid cancer is unclear. In the present work, we explored the expression of LINC-PINT in 60 paired thyroid cancer and adjacent normal tissues. The clinical significance and biological function of LINC-PINT in thyroid cancer were determined. LINC-PINT expression was downregulated in thyroid cancer relative to adjacent normal tissues (p = 0.0002). Low expression of LINC-PINT was significantly associated with advanced tumor node metastasis (TNM) stage (p = 0.0306) and lymph node metastasis (p = 0.0359). Ectopic expression of LINC-PINT suppressed the proliferation, invasion, and tumorigenesis of thyroid cancer cells. Mechanistically, LINC-PINT associated with and downregulated microRNA (miR)-767-5p. Moreover, LINC-PINT overexpression relieved miR-767-5p-mediated repression of ten-eleven translocation 2 (TET2). miR-767-5p promoted aggressiveness of thyroid cancer, which was reversed by overexpression of TET2. Coexpression of miR-767-5p or depletion of TET2 rescued the inhibitory effect of LINC-PINT on thyroid cancer cell proliferation and invasion. In addition, there was a negative correlation between miR-767-5p and LINC-PINT in thyroid cancer ( = -0.34772, p = 0.01789). Taken together, LINC-PINT functions as a tumor suppressor in thyroid cancer via the miR-767-5p/TET2 axis, representing a potential therapeutic target for thyroid cancer.
PubMed: 33230437
DOI: 10.1016/j.omtn.2020.05.033 -
Hepatology (Baltimore, Md.) Jul 2021HCV often causes chronic infection in liver, cirrhosis, and, in some instances, HCC. HCV encodes several factors' those impair host genes for establishment of chronic... (Observational Study)
Observational Study
BACKGROUND AND AIMS
HCV often causes chronic infection in liver, cirrhosis, and, in some instances, HCC. HCV encodes several factors' those impair host genes for establishment of chronic infection. The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. However, their role in virus replication and underlying diseases is poorly understood. In this study, we have shown that HCV exploits lncRNA long intergenic nonprotein-coding RNA, p53 induced transcript (Linc-Pint) in hepatocytes for enhancement of lipogenesis.
APPROACH AND RESULTS
We identified a lncRNA, Linc-Pint, which is significantly down-regulated in HCV-replicating hepatocytes and liver specimens from HCV infected patients. Using RNA pull-down proteomics, we identified serine/arginine protein specific kinase 2 (SRPK2) as an interacting partner of Linc-Pint. A subsequent study demonstrated that overexpression of Linc-Pint inhibits the expression of lipogenesis-related genes, such as fatty acid synthase and ATP-citrate lyase. We also observed that Linc-Pint significantly inhibits HCV replication. Furthermore, HCV-mediated enhanced lipogenesis can be controlled by exogenous Linc-Pint expression. Together, our results suggested that HCV-mediated down-regulation of Linc-Pint enhances lipogenesis favoring virus replication and liver disease progression.
CONCLUSIONS
We have shown that SRPK2 is a direct target of Linc-Pint and that depletion of SRPK2 inhibits lipogenesis. Our study contributes to the mechanistic understanding of the role of Linc-Pint in HCV-associated liver pathogenesis.
Topics: Biopsy; Cell Line; Disease Progression; Down-Regulation; Hepacivirus; Hepatitis C, Chronic; Hepatocytes; Host-Pathogen Interactions; Humans; Lipogenesis; Liver; Protein Serine-Threonine Kinases; RNA, Long Noncoding
PubMed: 33236406
DOI: 10.1002/hep.31656 -
Journal of Orthopaedic Surgery and... Aug 2023Lumbar disc herniation (LDH) is a complex spinal disease, with multiple genetic polymorphisms being related to its risk. Nevertheless, the role of LINC-PINT...
BACKGROUND
Lumbar disc herniation (LDH) is a complex spinal disease, with multiple genetic polymorphisms being related to its risk. Nevertheless, the role of LINC-PINT polymorphisms in LDH risk has remained unknown. Therefore, this study aimed to investigate the association between LINC-PINT polymorphisms and LDH risk.
METHODS
DNA was extracted from 504 LDH patients and 500 healthy controls. Three single nucleotide polymorphisms (SNPs) in LINC-PINT were selected and genotyped using Agena MassARRAY. We used logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) under multiple genetic models to evaluate the association between LINC-PINT polymorphisms and LDH risk. Haploview 4.2 and SNPStats software were used to evaluate the linkage strength of SNPs and the correlation between haplotypes and LDH risk. The impact of SNP-SNP interactions on LDH risk was analyzed using multi-factor dimensionality reduction (MDR).
RESULTS
Results showed that rs157916 (G vs. A: OR = 1.23, FDR-p = 0.029) and rs7801029 (G vs. C: OR = 1.39, FDR-p = 0.006; GG vs. CC: OR = 2.34, FDR-p = 0.038; recessive: OR = 2.13, FDR-p = 0.045; additive: OR = 1.39, FDR-p = 0.030) were associated with an increased risk of LDH. Furthermore, LINC-PINT rs157916 and rs780129 were found to be significantly associated with LDH risk in males. The "GGG" haplotype was associated with increased LDH risk (OR = 1.41, FDR-p = 0.006). MDR analysis indicated that the interaction between rs7801029 and rs16873842 was associated with an increased risk of LDH (OR = 1.47, p = 0.004). Additionally, there were significant differences in C-reactive protein levels among different genotypes of rs157916 and rs780129 (p < 0.05).
CONCLUSION
This study suggests that LINC-PINT gene polymorphisms (rs157916 and rs7801029) are considered risk factors for LDH in the Chinese Han population and provide a scientific basis for early screening, prevention, and diagnosis of LDH.
Topics: Humans; Male; Case-Control Studies; China; East Asian People; Gene Frequency; Genetic Predisposition to Disease; Intervertebral Disc Displacement; Lumbar Vertebrae; Polymorphism, Single Nucleotide; RNA, Long Noncoding
PubMed: 37553573
DOI: 10.1186/s13018-023-04052-5 -
Biomedicine & Pharmacotherapy =... Nov 2021Cancer involves complex etiology factors, multiple stages, and intricate gene mutations. Long non-coding RNAs (lncRNAs) are implicated as molecular mechanisms underlying... (Review)
Review
Cancer involves complex etiology factors, multiple stages, and intricate gene mutations. Long non-coding RNAs (lncRNAs) are implicated as molecular mechanisms underlying human genomic activity in various physiologic and pathophysiologic conditions. However, the sophisticated modifications and regulatory processes linking lncRNAs to cancer initiation and progression have not yet been fully explored. Long intragenic non-coding RNA p53-induced transcript (LINC-PINT) is an lncRNA that functions as a tumor suppressor gene involved in various tumors and malignant activities. LINC-PINT is downregulated in nasopharyngeal cancer, renal carcinoma, non-small cell lung cancer, glioblastoma, thyroid cancer, retinoblastoma, ovarian cancer, breast cancer, esophageal squamous cell carcinoma, osteosarcoma, melanoma, and gastric cancer. Furthermore, decreased LINC-PINT expression predicts poor prognosis and advanced clinical tumor stages. Together, these studies indicate that LINC-PINT could serve as a diagnostic and prognostic indicator in cancer. The specific lncRNA regulatory mechanism of LINC-PINT may also be a novel target for cancer therapies.
Topics: Animals; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Prognosis; RNA, Long Noncoding; Signal Transduction
PubMed: 34474342
DOI: 10.1016/j.biopha.2021.112127