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Cell Death & Disease May 2021Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and...
Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.
Topics: Cell Line, Tumor; Cell Proliferation; DNA Damage; DNA Repair; DNA-Activated Protein Kinase; Humans; Nasopharyngeal Neoplasms; RNA, Long Noncoding
PubMed: 33963177
DOI: 10.1038/s41419-021-03728-2 -
Scientific Reports Jan 2024The association between sarcopenia and OA still presents many uncertainties. We aimed to assess whether sarcopenia is associated with occurrence of OA in US adults. We...
The association between sarcopenia and OA still presents many uncertainties. We aimed to assess whether sarcopenia is associated with occurrence of OA in US adults. We conducted a cross-sectional study consisting of 11,456 participants from National Health and Nutrition Examination Survey 1999-2006. Sarcopenia was defined by a low muscle mass. The skeletal muscle index (SMI) was calculated as the appendicular skeletal muscle mass divided by body mass indexes (BMI) or body weight. OA status was assessed by using self-reported questionnaire. We evaluated the association between sarcopenia and OA using multivariate regression models. In addition, subgroup and interaction analysis were performed. Sarcopenia was associated with OA when it was defined by the BMI-adjusted SMI (OR = 1.23 [95% CI, 1.01, 1.51]; P = 0.038) and defined by the weight-adjusted SMI (OR = 1.30 [95% CI, 1.10, 1.55]; P = 0.003). Subgroup and interaction analysis found that the strongest positive association mainly exists in smoker (OR = 1.54 [95% CI, 1.21, 1.95], Pint = 0.006), and this association is not significant in other groups. In conclusion, we found that sarcopenia was associated with occurrence of OA. Subgroup analysis revealed that the association between sarcopenia and OA was more pronounced in smoker. Further well-designed prospective cohort studies are needed to assess our results.
Topics: Adult; Humans; Sarcopenia; Cross-Sectional Studies; Nutrition Surveys; Prospective Studies; Muscle, Skeletal; Osteoarthritis
PubMed: 38167445
DOI: 10.1038/s41598-023-50528-z -
Cancer Management and Research 2021This study mainly explored the expression level of LINC-PINT in bladder cancer and its relationship with prognosis. Meanwhile, the effect of LINC-PINT on the biological...
BACKGROUND
This study mainly explored the expression level of LINC-PINT in bladder cancer and its relationship with prognosis. Meanwhile, the effect of LINC-PINT on the biological function of bladder cancer was also explored.
METHODS
The expression levels of LINC-PINT and miR-155-5p were detected by qRT-PCR. The prognostic significance of LINC-PINT in bladder cancer was studied by the Kaplan-Meier curve and Log rank test. CCK-8 and Transwell assays were used to analyze the proliferation, migration, and invasion ability. The targeting relationship between LINC-PINT and miR-155-5p was analyzed using bioinformatics and dual-luciferase reporter assays.
RESULTS
The expression of LINC-PINT was downregulated in bladder cancer tissues and cell lines, and miR-155-5p showed the opposite trend in bladder cancer tissues. Kaplan-Meier curve proved that the patients with low LINC-PINT expression had a lower five-year survival rate and the Log rank test displayed that LINC-PINT was a prognostic factor of BC. CCK-8 and Transwell results showed that LINC-PINT could inhibit the ability of proliferation, migration, and invasion. LINC-PINT was proved to target miR-155-5p in bladder cancer. Dual-luciferase reporter gene assay showed that the relative luciferase activity of overexpression miR-155-5p co-transfected with LINC-PINT-wt was significantly lower. LINC-PINT was negatively correlated with miR-155-5p.
CONCLUSION
LINC-PINT is a potential prognostic marker of bladder cancer, and the up-regulation of Lin-PINT can inhibit the proliferation, invasion, and migration of bladder cancer cells by targeting miR-155-5p.
PubMed: 34103994
DOI: 10.2147/CMAR.S305547 -
Plasma and tumor levels of Linc-pint are diagnostic and prognostic biomarkers for pancreatic cancer.Oncotarget Nov 2016Long intergenic non-protein coding RNA, p53 induced transcript (Linc-pint) is a long noncoding RNA (lncRNA) that regulates tumor cell viability and proliferation. We...
Long intergenic non-protein coding RNA, p53 induced transcript (Linc-pint) is a long noncoding RNA (lncRNA) that regulates tumor cell viability and proliferation. We used qRT-PCR and RNA FISH analysis to evaluate Linc-pint levels in the plasma and tumor tissues of pancreatic cancer (PCa) patients. Our data demonstrate that Linc-pint expression is lower in plasma samples from PCa patients than from healthy individuals, and indicate that plasma Linc-pint levels are more sensitive than CA19-9 for detecting PCa. Our data also show that Linc-pint levels are lower in PCa tumors than in adjacent tissues, carcinoma of the ampulla of Vater (CAV) and cholangiocarcinoma (CCA), and suggest that Linc-pint could be used for distinguishing the cause of malignant obstructive jaundice. Low plasma Linc-pint levels correlate with tumor recurrence, while low tumor Linc-pint levels correlate with poor prognosis for PCa patients after pancreatectomy. These results thus indicate that low plasma Linc-pint expression could serve as a minimally invasive biomarker for early PCa detection, and that low Linc-pint levels in PCa tumors could be used for predicting patient prognosis.
Topics: Adult; Aged; Biomarkers, Tumor; CA-19-9 Antigen; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Prognosis; RNA, Long Noncoding
PubMed: 27708234
DOI: 10.18632/oncotarget.12365 -
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 -
Frontiers in Molecular Biosciences 2023Long noncoding RNAs (lncRNAs) possess the potential for therapeutic targeting to treat many disorders, including cancers. Several RNA-based therapeutics (ASOs and small...
Long noncoding RNAs (lncRNAs) possess the potential for therapeutic targeting to treat many disorders, including cancers. Several RNA-based therapeutics (ASOs and small interfering RNAs) have gained FDA approval over the past decade. And with their potent effects, lncRNA-based therapeutics are of emerging significance. One important lncRNA target is LINC-PINT, with its universalized functions and relationship with the famous tumor suppressor gene Establishing clinical relevance, much like p53, the tumor suppressor activity of LINC-PINT is implicated in cancer progression. Moreover, several molecular targets of LINC-PINT are directly or indirectly used in routine clinical practice. We further associate LINC-PINT with immune responses in colon adenocarcinoma, proposing the potential utility of LINC-PINT as a novel biomarker of immune checkpoint inhibitors. Collectively, current evidence suggests LINC-PINT can be considered for use as a diagnostic/prognostic marker for cancer and several other diseases.
PubMed: 37006616
DOI: 10.3389/fmolb.2023.1097694 -
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 -
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 -
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 -
Cardiovascular Diabetology Sep 2022Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF.
METHODS
This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT03313752).
RESULTS
16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 μmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 μmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; p = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; p = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054).
CONCLUSIONS
SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction. Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752.
Topics: Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Glucosides; Heart Failure; Humans; Positron Emission Tomography Computed Tomography; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 36057768
DOI: 10.1186/s12933-022-01607-4