Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma

Rothzerg, Emel; Ho, Xuan Dung; Xu, Jiake; Wood, David; Märtson, Aare; Kõks, Sulev

doi:10.3390/genes12081132

Cited by 33 publications

(27 citation statements)

References 75 publications

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“…It was reported that HIF1A-AS2 is up-regulated in GC tumorous tissues, and its overexpression promotes gastric cancer cell proliferation and metastasis and indicates poor prognosis ( Mu et al, 2021 ; Chen et al, 2015 ). RP11-366L20.2, also known as HMGA2-AS1, has been recognized as an oncogene in pancreatic cancer ( Ros et al, 2019 ) and osteosarcoma ( Rothzerg et al, 2021 ). However, there are few studies on the role of RP11-366L20.2 in gastric cancer, and it is worthy of further study.…”

Section: Discussionmentioning

confidence: 99%

lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer

Nai

Zeng

et al. 2022

Front. Cell Dev. Biol.

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Gastric carcinoma is the fourth most prevalent cause of cancer-related deaths worldwide because of dismal prognosis and few therapeutic options. Accumulated studies have indicated that targeting lysyl oxidase (LOX) family members may serve as an anticancer strategy. Nevertheless, the specific mechanisms of LOX in stomach carcinoma are still unclear. In this study, we demonstrated that LOX is significantly different in 13 types of cancers and may act as a potential therapeutic target, especially in stomach carcinoma. Moreover, overexpression of LOX in gastric carcinoma was validated by multiple databases and contributed to the poor overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) of stomach adenocarcinoma (STAD) patients. Next, based on the ceRNA hypothesis, the HIF1A-AS2/RP11-366L20.2-miR-29c axis was characterized as the upstream regulatory mechanism of LOX gene overexpression in gastric cancer by combining correlation analysis, expression analysis, and survival analysis. Finally, we illustrated that LOX gene overexpression leads to dismal prognosis of gastric cancer, perhaps through promoting M2 macrophage polarization and tumor immune escape and enhancing drug resistance of tumor cells to chemotherapeutic drugs. Our research demonstrate that LOX may be potentially applied as a novel prognostic marker and targeting inhibition of LOX holds promise as a treatment strategy for gastric cancer.

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Section: Discussionmentioning

confidence: 99%

lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer

Nai

Zeng

et al. 2022

Front. Cell Dev. Biol.

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“…Hence it is important to understand and correlate expression of MCTs and ECMs in different compartments. Our analysis revealed nine differentially expressed MCT genes in both stromal and epithelial samples including the upregulated thyroid hormone (TH) transporters MCT8 (SLC16A12) and MCT10 (SLC16A10), monocarboxylate transporter MCT2 (SLC16A7), MCT6 (SLC16A5) with potential role in glucose and lipid metabolism, and an lncRNA SLC16A1-AS1 previously identified as a prognostic or diagnostic biomarker in a number of cancers [13,[47][48][49][50][51][52][53][54]. To our knowledge, the upregulation of the TH transporters in the stromal-epithelial samples has not been highlighted previously.…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, better understanding of the molecular mechanisms involved in contribution of THs to pancreatic cancer is needed. The lncRNA SLC16A1-AS1 has previously been found to be upregulated in osteosarcoma, glioblastoma and oral squamous cell carcinoma [50, 52, 63], downregulated in non-small cell lung cancer and cervical squamous cell carcinoma [19, 49], and show conflicting expression profile in hepatocellular carcinoma [51, 53, 54]. This is the first study highlighting differential expression of SLC16A1-AS1 in PDAC showing lower levels of expression in epithelial relative to stromal compartment.…”

Section: Discussionmentioning

confidence: 99%

Monocarboxylate Transporters are Involved in Extracellular Matrix Remodelling in Pancreatic Ductal Adenocarcinoma

Ufuk

Garner

Stevens

et al. 2022

Preprint

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a five-year survival rate of <8%. PDAC is characterised by desmoplasia with abundant extracellular matrix (ECM) rendering current therapies ineffective. Monocarboxylate transporters (MCTs) are key regulators of cellular metabolism and are upregulated in different cancers, however their role in PDAC desmoplasia is little understood. Here, we investigated MCT and ECM gene expression in primary PDAC patient biopsies using RNA-sequencing data obtained from Gene Expression Omnibus. We generated a hypernetwork model from these data to investigate whether a causal relationship exists between MCTs and ECMs. Our analysis of stromal and epithelial tissues (n=189) revealed 9 differentially expressed MCTs, including upregulation of SLC16A2/6/10 and the non-coding SLC16A1-AS1, and 502 ECMs including collagens, laminins, and ECM remodelling enzymes (false discovery rate<0.05). Causal hypernetwork analysis demonstrated a bidi-rectional relationship between MCTs and ECMs; 4 MCT and 255 ECM-related transcripts correlated with 90% of differentially expressed ECMs (n=376) and MCTs (n=7), respectively. The hypernetwork model was robust, established by two independent approaches involving iterated sampling and silencing of indirect interactions in the network. This transcriptomic analysis highlights the role of MCTs in PDAC desmoplasia via associations with ECMs, opening novel treatment pathways to improve patient survival.

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“…Hence, it is important to understand and correlate the expression of MCTs and ECMs in different compartments. Our analysis revealed nine differentially expressed MCT genes in both stromal and epithelial samples, including the upregulated thyroid hormone (TH) transporters MCT8 ( SLC16A12 ) and MCT10 ( SLC16A10 ), monocarboxylate transporter MCT2 ( SLC16A7 ), MCT6 ( SLC16A5 ) with a potential role in glucose and lipid metabolism, and an lncRNA SLC16A1-AS1 previously identified as a prognostic or diagnostic biomarker in a number of cancers [ 20 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. To our knowledge, the upregulation of the TH transporters in the stromal–epithelial samples has not been highlighted previously.…”

Section: Discussionmentioning

confidence: 99%

Monocarboxylate Transporters Are Involved in Extracellular Matrix Remodelling in Pancreatic Ductal Adenocarcinoma

Ufuk

Garner

Stevens

et al. 2022

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a five-year survival rate of <8%. PDAC is characterised by desmoplasia with an abundant extracellular matrix (ECM) rendering current therapies ineffective. Monocarboxylate transporters (MCTs) are key regulators of cellular metabolism and are upregulated in different cancers; however, their role in PDAC desmoplasia is little understood. Here, we investigated MCT and ECM gene expression in primary PDAC patient biopsies using RNA-sequencing data obtained from Gene Expression Omnibus. We generated a hypernetwork model from these data to investigate whether a causal relationship exists between MCTs and ECMs. Our analysis of stromal and epithelial tissues (n = 189) revealed nine differentially expressed MCTs, including the upregulation of SLC16A2/6/10 and the non-coding SLC16A1-AS1, and 502 ECMs, including collagens, laminins, and ECM remodelling enzymes (false discovery rate < 0.05). A causal hypernetwork analysis demonstrated a bidirectional relationship between MCTs and ECMs; four MCT and 255 ECM-related transcripts correlated with 90% of the differentially expressed ECMs (n = 376) and MCTs (n = 7), respectively. The hypernetwork model was robust, established by iterated sampling, direct path analysis, validation by an independent dataset, and random forests. This transcriptomic analysis highlights the role of MCTs in PDAC desmoplasia via associations with ECMs, opening novel treatment pathways to improve patient survival.

show abstract

Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma

Cited by 33 publications

References 75 publications

lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer

lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer

Monocarboxylate Transporters are Involved in Extracellular Matrix Remodelling in Pancreatic Ductal Adenocarcinoma

Monocarboxylate Transporters Are Involved in Extracellular Matrix Remodelling in Pancreatic Ductal Adenocarcinoma

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