Overexpression of lncRNA SLC26A4-AS1 inhibits papillary thyroid carcinoma progression through recruiting ETS1 to promote ITPR1-mediated autophagy.
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PROVIDER: S-EPMC9077309 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
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Overexpression of lncRNA SLC26A4-AS1 inhibits papillary thyroid carcinoma progression through recruiting ETS1 to promote ITPR1-mediated autophagy.
Journal of cellular and molecular medicine 20220501 9
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Project description:Papillary thyroid carcinoma (PTC), accounting for approximately 85% cases of thyroid cancer, is a common endocrine tumour with a relatively low mortality but an alarmingly high rate of recurrence or persistence. Long non-coding RNAs (lncRNAs) is emerging as a critical player modulating diverse cellular mechanisms correlated with the progression of various cancers, including PTC. Herein, we aimed to investigate the role of lncRNA SLC26A4-AS1 in regulating autophagy and tumour growth during PTC progression. Initially, ITPR1 was identified by bioinformatics analysis as a differentially expressed gene. Then, Western blot and RT-qPCR were conducted to determine the expression of ITPR1 and SLC26A4-AS1 in PTC tissues and cells, both of which were found to be poorly expressed in PTC tissues and cells. Then, we constructed ITPR1-overexpressing cells and revealed that ITPR1 overexpression could trigger the autophagy of PTC cells. Further, we performed a series of gain- and loss-of function experiments. The results suggested that silencing of SLC26A4-AS1 led to declined ITPR1 level, up-regulation of ETS1 promoted ITPR1 expression, and either ETS1 knockdown or autophagy inhibitor Bafilomycin A1 could mitigate the promoting effects of SLC26A4-AS1 overexpression on PTC cell autophagy. In vivo experiments also revealed that SLC26A4-AS1 overexpression suppressed PTC tumour growth. In conclusion, our study elucidated that SLC26A4-AS1 overexpression promoted ITPR1 expression through recruiting ETS1 and thereby promotes autophagy, alleviating PTC progression. These finding provides insight into novel target therapy for the clinical treatment of PTC.
| S-EPMC8419164 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) were recently shown to have potential in the diagnosis and prognosis for numerous cancers. lncRNA GAS8-AS1 is decreased in papillary thyroid cancer (PTC) tissue, but its plasma expression and clinical value in patients with PTC remain unknown.We investigated the expression profile of plasma GAS8-AS1 in 97 patients with PTC and 39 patients with nodular goiter by quantitative real-time polymerase chain reaction.GAS8-AS1 expression in plasma was downregulated in patients with PTC in comparison with those in nodular goiters (P < 0.001). A low level of plasma GAS8-AS1 expression was correlated with lymph node metastasis (LNM) (P < 0.001). Multivariate analysis showed that a reduced GAS8-AS1 level in plasma was associated with LNM (P < 0.05). The area under the receiver operating characteristic curve for GAS8-AS1 was 0.746 in LNM prediction (P < 0.001).The present study indicates that circulating GAS8-AS1 is a potential biomarker for PTC diagnosis and LNM prediction.
| S-EPMC5525075 | biostudies-other
Project description:Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.
| S-EPMC10719255 | biostudies-literature
Project description:BackgroundThe incidence and mortality of thyroid cancer (TC) has been steadily rising in the past decades. It is imperative to have a better understanding of the molecular mechanisms underlying TC development and identify novel therapeutic targets. This study characterized the role of lncRNA CALML3-AS1 (CALML3-AS1) in the development of papillary thyroid cancer (PTC).MethodRelated mRNAs expression were validated in the tumor and adjacent normal tissues from 52 PTC patients and PTC cell lines by qRT-PCR. Expression of RBM38 was detected by Western blot. We have also conducted CCK-8 and colony formation assays were used to detect the effect of CALML3-AS1 on cell proliferation, Transwell assay was utilized to evaluate cell migration and invasion, apoptosis detected by flow cytometry assay, RNA pull-down and luciferase assays were performed to validate gene predictions.ResultsThe results indicated that the expression of both CALML3A-S1 and RBM38 were significantly downregulated in PTC tissues (p < 0.01), while the expression of miR-20a-5p was increased in PTC (p < 0.01). Functionally, CALML3-AS1 overexpression inhibited PTC cell proliferation in vitro and in vivo. Mechanistically, CALML 3-AS1 sponged miR-20a-5p, which in turn leads to the suppression of RBM38 expression and PTC progression.ConclusionsCALML3-AS1 functions as a ceRNA for miR-20a-5p in the regulation of the expression of RBM38 in PTC. Higher level of CALML3-AS1 serves as a good prognostic indicator of survival in PTC patients. Targeting CALML3-AS1/ miR-20a-5p/RBM38 axis may represent a novel therapeutic strategy in the treatment of PTC.
| S-EPMC8966157 | biostudies-literature
Project description:BackgroundPapillary thyroid cancer (PTC) is the most common type of cancer of the endocrine system. Long noncoding RNAs (lncRNAs) are emerging as a novel class of gene expression regulators associated with tumorigenesis. Through preexisting databases available for differentially expressed lncRNAs in PTC, we uncovered that lncRNA OIP5-AS1 was significantly upregulated in PTC tissues. However, the function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood.MethodsExpression of lncRNA OIP5-AS1 and miR-98 in PTC tissue and cells were measured by quantitative real-time PCR (qRT-PCR). And expression of METTL14 and ADAMTS8 in PTC tissue and cells were measured by qRT-PCR and western blot. The biological functions of METTL14, OIP5-AS1, and ADAMTS8 were examined using MTT, colony formation, transwell, and wound healing assays in PTC cells. The relationship between METTL14 and OIP5-AS1 were evaluated using RNA immunoprecipitation (RIP) and RNA pull down assay. And the relationship between miR-98 and ADAMTS8 were examined by luciferase reporter assay. For in vivo experiments, a xenograft model was used to investigate the effects of OIP5-AS1 and ADAMTS8 in PTC.ResultsFunctional validation revealed that OIP5-AS1 overexpression promotes PTC cell proliferation, migration/invasion in vitro and in vivo, while OIP5-AS1 knockdown shows an opposite effect. Mechanistically, OIP5-AS1 acts as a target of miR-98, which activates ADAMTS8. OIP5-AS1 promotes PTC cell progression through miR-98/ADAMTS8 and EGFR, MEK/ERK pathways. Furthermore, RIP and RNA pull down assays identified OIP5-AS1 as the downstream target of METTL14. Overexpression of METTL14 suppresses PTC cell proliferation and migration/invasion through inhibiting OIP5-AS1 expression and regulating EGFR, MEK/ERK pathways.ConclusionsCollectively, our findings demonstrate that OIP5-AS1 is a METTL14-regulated lncRNA that plays an important role in PTC progression and offers new insights into the regulatory mechanisms underlying PTC development.
| S-EPMC8206147 | biostudies-literature
Project description:The long non-coding (lnc)RNA pre-ribosomal RNA antisense transcripts (PAPAS) can repress ribosomal RNA synthesis, although its role in human disease is currently unknown. The present study aimed to investigate the function of PAPAS in papillary thyroid carcinoma (PTC). PAPAS was downregulated, while the lncRNA HOXA transcript at the distal tip (HOTTIP) was upregulated in patients with PTC. PAPAS and HOTTIP were inversely associated in PTC. PAPAS overexpression led to the downregulation of HOTTIP in PTC cells, while PAPAS expression was not significantly affected by HOTTIP overexpression, suggesting that PAPAS was upstream of HOTTIP. PAPAS expression level decreased, while HOTTIP expression level increased with the increase of clinical staging. PAPAS overexpression led to the inhibition of cell proliferation, while HOTTIP overexpression increased proliferation of PTC cells, and HOTTIP overexpression decreased the effects of PAPAS overexpression. lncRNA PAPAS overexpression may inhibit tumor growth in papillary thyroid carcinoma by downregulating lncRNA HOTTIP.
| S-EPMC7039133 | biostudies-literature
Project description:Pulmonary arterial hypertension (PAH) is a life-threatening disease featured with elevated pulmonary vascular resistance and progressive pulmonary vascular remodelling. It has been demonstrated that lncRNA PAXIP1-AS1 could influence the transcriptome in PAH. However, the exact molecular mechanism of PAXIP1-AS1 in PAH pathogenesis remains largely unknown. In this study, in vivo rat PAH model was established by monocrotaline (MCT) induction and hypoxia was used to induce in vitro PAH model using human pulmonary artery smooth muscle cells (hPASMCs). Histological examinations including H&E, Masson's trichrome staining and immunohistochemistry were subjected to evaluate the pathological changes of lung tissues. Expression patterns of PAXIP1-AS1 and RhoA were assessed using qRT-PCR and Western blotting, respectively. CCK-8, BrdU assay and immunofluorescence of Ki67 were performed to measure the cell proliferation. Wound healing and transwell assays were employed to evaluate the capacity of cell migration. Dual-luciferase reporter assay, co-immunoprecipitation, RIP and CHIP assays were employed to verify the PAXIP1-AS1/ETS1/WIPF1/RhoA regulatory network. It was found that the expression of PAXIP1-AS1 and RhoA was remarkably higher in both lung tissues and serum of MCT-induced PAH rats, as well as in hypoxia-induced hPASMCs. PAXIP1-AS1 knockdown remarkably suppressed hypoxia-induced cell viability and migration of hPASMCs. PAXIP1-AS1 positively regulated WIPF1 via recruiting transcriptional factor ETS1, of which knockdown reversed PAXIP1-AS1-mediated biological functions. Co-immunoprecipitation validated the WIPF1/RhoA interaction. In vivo experiments further revealed the role of PAXIP1-AS1 in PAH pathogenesis. In summary, lncRNA PAXIP1-AS1 promoted cell viability and migration of hPASMCs via ETS1/WIPF1/RhoA, which might provide a potential therapeutic target for PAH treatment.
| S-EPMC8335679 | biostudies-literature
Project description:The present study was designed to assess the protein expression of the autophagy-associated genes, Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)-II, as well as the association with clinicopathological features in papillary thyroid carcinoma (PTC). A total of 50 subjects were recruited, including 50 human PTC samples and paired adjacent noncancerous tissue samples. The protein expression of Beclin-1 and LC3-II was analyzed using immunohistochemistry and western blotting. Beclin-1 and LC3-II expression in PTC tissues significantly reduced compared with normal tissues (P<0.05). Expression of Beclin-1 and LC3-II was associated with lymph node metastasis of PTC (P<0.05), but had no association with age, gender, tumor size, tumor number and Tumor-Node-Metastasis stage (P>0.05). Expression of Beclin-1 and LC3-II were positively correlated (r=0.327;P=0.020) in PTC. In conclusion, the activity of autophagy was declined in PTC; this decrease in autophagic capacity may be associated with tumorigenesis and the development of PTC.
| S-EPMC5494896 | biostudies-other
Project description:The current focus in the treatment of papillary thyroid carcinoma (PTC) is tumor progression. The aim of this study was to build RNA-based classifiers and develop a comprehensive model to provide progression-free interval (PFI) risk prediction for PTC. The RNAseq data, miRNAseq data, and clinical information of PTC were downloaded from The Cancer Genome Atlas database. Based on the differently expressed RNAs, the least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to build the RNA-based classifiers for PFI of the patients with PTC. A 6-messenger RNA (mRNA)-based classifier, a 5-long non-coding RNA (lncRNA)-based classifier, and a 4-microRNA (miRNA)-based classifier were constructed to predict the PFI. Patients with high risk based on the constructed RNA-based classifiers had worse prognosis in Kaplan-Meier curve analysis with log-rank test. The areas under the curves of the first, third, and fifth years in the training and testing set were 0.83, 0.82, and 0.82 and 0.67, 0.72, and 0.73 for the 6-mRNA-based classifier, respectively; 0.75, 0.84, and 0.85 and 0.71, 0.67, and 0.71 for the 5-lncRNA-based classifier, respectively; and 0.70, 0.77, and 0.79 and 0.74, 0.67, and 0.66 for the 4-miRNA-based classifier, respectively. The prediction capability of the three RNA-based classifiers was superior to the TNM stage system. Furthermore, a nomogram based on the verified independent prognostic factors was established for the prognostic prediction. The C-index and calibration plots indicated good predictive accuracy of the nomogram. In summary, the 6-mRNA-based classifier and 5-lncRNA-based classifier constructed in this study were independent prognostic factors for PTC.
| S-EPMC7417634 | biostudies-literature
Project description:CD73 is involved in tumor immune escape and promotes the growth and progression of cancer cells. The functional role of CD73 expression in papillary thyroid carcinoma (PTC) has not yet been established. In 511 patients with PTC, immunohistochemistry for CD73 on tissue microarrays showed that the high expression of CD73 was associated with an aggressive histologic variant (p = 0.002), extrathyroidal extension (p < 0.001), lymph node metastasis (p < 0.001), and BRAFV600E mutation (p = 0.015). Survival analysis results showed that patients with high CD73 expression had worse recurrence-free survival (p = 0.023). CD73 inhibitors induced G1 cell cycle arrest and apoptosis, inhibited the migration and invasion of PTC cells, and suppressed tumor growth in PTC xenograft nude mice. High expression of CD73 (NT5E) mRNA was associated with unfavorable clinicopathologic characteristics, the abundance of Tregs and dendritic cells, depletion of natural killer (NK) cells, and high expression of immune checkpoint genes and epithelial-to-mesenchymal transition-related genes in The Cancer Genome Atlas (TCGA) dataset. Taken together, CD73 expression promotes tumor progression and predicts low recurrence-free survival. Targeting the CD73-adenosine axis in the tumor microenvironment offers an attractive pathway for therapeutic strategies aimed at advanced PTC.
| S-EPMC7603384 | biostudies-literature