In Silico and In Vitro Analyses of LncRNAs as Potential Regulators in the Transition from the Epithelioid to Sarcomatoid Histotype of Malignant Pleural Mesothelioma (MPM)

Our plain-English summary of In Silico and In Vitro Analyses of LncRNAs as Potential Regulators in the Transition from the Epithelioid to Sarcomatoid Histotype of Malignant Pleural Mesothelioma (MPM), by A.S. Singh, R. Heery, S.G. Gray (International Journal of Molecular Sciences, 2018).

The study

• Authors: A.S. Singh, R. Heery, S.G. Gray
• Journal: International Journal of Molecular Sciences
• Published: 2018;19(5)
• Type of article: Review
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare malignancy, with extremely poor survival rates. At present, treatment options are limited, with no second line chemotherapy for those who fail first line therapy. Extensive efforts are ongoing in a bid to characterise the underlying molecular mechanisms of mesothelioma. Recent research has determined that between 70⁻90% of our genome is transcribed. As only 2% of our genome is protein coding, the roles of the remaining proportion of non-coding RNA in biological processes has many applications, including roles in carcinogenesis and epithelial⁻mesenchymal transition (EMT), a process thought to play important roles in MPM pathogenesis. Non-coding RNAs can be separated loosely into two subtypes, short non-coding RNAs (<200 nucleotides) or long (>200 nucleotides). A significant body of evidence has emerged for the roles of short non-coding RNAs in MPM. Less is known about the roles of long non-coding RNAs (lncRNAs) in this disease setting. LncRNAs have been shown to play diverse roles in EMT, and it has been suggested that EMT may play a role in the aggressiveness of MPM histological subsets. In this report, using both in vitro analyses on mesothelioma patient material and in silico analyses of existing RNA datasets, we posit that various lncRNAs may play important roles in EMT within MPM, and we review the current literature regarding these lncRNAs with respect to both EMT and MPM.

In plain English

This review also reported new laboratory measurements and dataset analyses. It covered long non-coding RNAs (lncRNAs) in malignant pleural mesothelioma (MPM) and epithelial–mesenchymal transition (EMT), proposed to underlie the shift from epithelioid to more aggressive sarcomatoid disease. Surgical tissue came from 17 MPM patients (7 epithelioid, 4 sarcomatoid, 6 biphasic) and 5 benign pleural samples at Glenfield Hospital, Leicester, UK. EGFR-AS1 was significantly higher in the 17 tumours than the 5 benign samples (one-tailed t-test, p = 0.0445). PCAT6 and ZEB2-AS1 used 16 tumours and 4 benign samples. PCAT6 was significantly higher in tumours overall; split by subtype, only the biphasic group differed significantly. ZEB2-AS1 appeared higher, but not significantly (one-tailed p = 0.0769). In The Cancer Genome Atlas dataset (87 mesotheliomas), higher H19 expression was associated with worse overall survival (p = 0.0016), as was higher HOTAIR. Higher CASC2 expression was associated with better survival (p = 0.000203). Asbestos exposure was not examined. The authors concluded that EMT-related lncRNAs are dysregulated in MPM and may be associated with more aggressive subtypes. They said the ZEB2-AS1 findings need validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of the literature combined with preliminary laboratory measurements (RT-PCR) on patient tissue and in silico analyses of existing public datasets
• Who was studied: Surgical tissue from 17 MPM patients (epithelioid 7, sarcomatoid 4, biphasic 6) and 5 benign pleural lesions, obtained at Glenfield Hospital, Leicester, UK. EGFR-AS1 and KDM5B were measured in 17 tumours and 5 benign samples. PCAT6 and ZEB2-AS1 were measured in 16 tumours and 4 benign samples. Existing datasets were also analysed: the Gordon et al. dataset and a TCGA mesothelioma dataset of 87 samples (epithelioid 57, biphasic 23, sarcomatoid 2, other 5).
• Exposure: Not studied. The article examined lncRNA expression in tumour tissue and reported no asbestos or other exposure data for the patients.
• Main results:
  • EGFR-AS1 was significantly higher in primary MPM (n = 17) than in benign pleura (n = 5) (p = 0.0445, one-tailed unpaired t-test).
  • KDM5B mRNA was significantly upregulated in primary MPM (n = 17) compared with benign pleura (n = 5).
  • PCAT6 was significantly elevated in tumours (n = 16) compared with benign pleura (n = 4) in the pooled comparison.
  • When the PCAT6 measurements were split by histological subtype, the elevation was significant only in the biphasic subset.
  • ZEB2-AS1 appeared elevated in tumours (n = 16) compared with benign pleura (n = 4), but the difference was not statistically significant (p = 0.0769, one-tailed unpaired t-test).
  • In the TCGA dataset, 8% of samples overexpressed HOTAIR, most of them biphasic, and higher HOTAIR expression was associated with worse overall survival.
  • In the TCGA dataset, high median H19 expression was associated with significantly worse overall survival (p = 0.0016).
  • In the TCGA dataset, high median CASC2 expression was associated with significantly better overall survival (p = 0.000203).
  • Analysis of the TCGA dataset found no alterations in PAX8-AS1 expression, although the authors' earlier publication had reported it as altered in MPM.
• The authors' conclusion: The authors concluded that lncRNAs associated with EMT are dysregulated in MPM and that their alteration may be associated with the more aggressive histological subtypes.
• Limitations the authors state:
  • The authors stated that the ZEB2-AS1 observations need further studies for validation.
  • The authors described their own laboratory data as preliminary.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Epithelioid, Sarcomatoid, Pleural Mesothelioma, Chemotherapy, Mesothelioma, Carcinogenesis.

Related studies

• Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM) — C.M. Wright, M.B. Kirschner, et al. (2013)
• The lncRNAs Gas5, MALAT1 and SNHG8 as diagnostic biomarkers for epithelial malignant pleural mesothelioma in Egyptian patients — D.M. Elkahwagy, C.J. Kiriacos, et al. (2024)
• Glycolysis-associated lncRNAs identify a subgroup of cancer patients with poor prognoses and a high-infiltration immune microenvironment — K.H. Ho, T.W. Huang, et al. (2021)
• Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma — M. Matboli, A.E. Shafei, et al. (2019)
• Downregulation of lncRNA PVT1 inhibits proliferation and migration of mesothelioma cells by targeting FOXM1 — Y. Fujii, V.J. Amatya, et al. (2022)
• Epithelioid peritoneal mesothelioma: a hybrid phenotype within a mesenchymal-epithelial/epithelial-mesenchymal transition framework — F. Bozzi, S. Brich, et al. (2016)

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