A preliminary study: is fibulin 1 a friend or an enemy that needs to be silenced with siRNAs for mesothelioma?

Our plain-English summary of A preliminary study: is fibulin 1 a friend or an enemy that needs to be silenced with siRNAs for mesothelioma?, by A. Aksoy, A. Tektemur, E. Melek, et al (Contemporary Oncology = Współczesna Onkologia, 2020).

The study

• Authors: A. Aksoy, A. Tektemur, E. Melek, M. Kayfeci, M.F. Uslu, U. Cosar, E. Onalan
• Journal: Contemporary Oncology = Współczesna Onkologia
• Published: 2020;24(4):241-246
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: The impaired balance between cell proliferation and cell death, followed the inability to receive the death signals, cells push towards the neoplasia pathway. Fibulin 1 (FBLN1) plays a role as a co-factor in the mechanism of action of a protease such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1), which has important roles in angiogenesis, can also act as both tumor suppressor gene (TSG) and an oncogene in the main constituent of the extra-cellular matrix. This preliminary study has investigated the effects of silencing FBLN1 with siRNA on autophagy, proliferation, apoptosis pathways in the MSM cell line.

Material And Methods: It was transfected siRNA specific to FBLN1 incubated MSM SPC212 cells, and compared with negative control siRNAs by a real-time polymerase chain reaction. It was determined apoptosis, proliferation, autophagy-related genes in mRNA levels.

Results: It was observed that increased anti-apoptosis genes, such as CASP2, CASP7, DDFA, and BCL2, anti-apoptotic gene, reduced APAF1, CASP8. Proliferation induced through while increased ADAMTS1, CDH1, CDH6, CLDN7, CSF3, MMP7, MMP13 genes. Autophagy increased via increasing MAP1LC3B, ATG-16L1 genes while decreased via suppressed ULK1, and ATG7 genes by silencing FBLN1 with siRNAs (p < 0.05).

Conclusions: Proliferation can be induction with silencing of FBLN1 with siRNA in processing mechanism MSM. It was concluded that FBLN1 could be act as pleiotropic on autophagy, and apoptosis pathways in proliferation processing for MSM. Therefore we think that FBLN1 acts like a TSG. FBLN1 can be considered as a targeted treatment option in advanced stage MSM.

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In plain English

This preliminary laboratory study used a single mesothelioma cell line called SPC212. It was not a study of people, and asbestos exposure was not studied. The authors used small interfering RNA (siRNA) to switch down a gene called fibulin 1 (FBLN1) and compared these cells with cells given a negative control siRNA. They then measured the expression (mRNA levels) of genes linked to cell death (apoptosis), cell growth and spread, and autophagy, a process in which cells break down their own parts. FBLN1 mRNA levels fell significantly, and the authors calculated the silencing at 81.3%. In the FBLN1 siRNA cells, several genes changed significantly. MMP7 had a fold change of 174.8532, CASP2 34.0598 and BCL2 3.4822, while ULK1 (0.1142), ATG7 (0.2017) and CASP8 (0.3392) were lower. The authors concluded that FBLN1 can act as a tumor suppressor gene in the early stages. They noted that they used only one cell line, did not check results with western blot, and that the work was preliminary. In places, the article's written descriptions of which genes rose or fell do not match its table.

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: preliminary laboratory (in vitro) cell-line experiment: gene silencing with siRNA compared with negative control siRNA, with gene expression measured at the mRNA level by real-time PCR
• Who was studied: One mesothelioma cell line, SPC212, grown in culture, in work by authors at Firat University, Elazig, Turkey; PCR measurements were repeated three times
• Exposure: No asbestos or fiber exposure was studied. The experimental condition was silencing of the FBLN1 gene with FBLN1-specific siRNA, compared with negative control siRNA
• Main results:
  • FBLN1 mRNA expression fell significantly in the siRNA cells compared with control (p = 0.0084); silencing was calculated as 81.3%
  • In the FBLN1 siRNA cells, the largest change in the table was for MMP7, with fold change 174.8532 (p = 0.003936)
  • In the FBLN1 siRNA cells, apoptosis-related genes with higher values in the table included CASP2 34.0598 (p = 0.004306), CASP7 22.6274 (p = 0.004565), BCL2 3.4822 (p = 0.014865) and DFFA 2.1435 (p = 0.045288)
  • In the FBLN1 siRNA cells, APAF1 (0.4698, p = 0.049464) and CASP8 (0.3392, p = 0.022406) were lower
  • In the FBLN1 siRNA cells, other growth and spread genes were higher: ADAMTS1 4.3169, CDH1 2.5315, CDH6 4.4076, CLDN7 5.2054, CSF3 4.3772 and MMP13 2.8284 (all p less than 0.05)
  • In the FBLN1 siRNA cells, autophagy genes ATG16L1 (3.6301) and MAP1LC3B (2.0994) were higher, while ULK1 (0.1142, p = 0.007178) and ATG7 (0.2017, p = 0.010764) were lower
• The authors' conclusion: The authors concluded that FBLN1 can act as a tumor suppressor gene in the early stages, and that silencing it increases tumor metastases and partially increases autophagy. They suggested that more extensive in vivo and in vitro studies might lead to new targeted therapy options.
• Limitations the authors state:
  • Only one mesothelioma cell line was used
  • Alternative splice variants of the genes, and genetic changes occurring as the cell line was passaged, were not examined
  • The study was preliminary, and apoptosis, autophagy and cell proliferation were not checked by western blot

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Angiogenesis, Tumor Suppressor Gene, Apoptosis.

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