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. 2023 Mar 29;12(7):1043. doi: 10.3390/cells12071043

Table 9.

Changes in gene regulation of different cancer cells exposed to microgravity conditions.

Cancer Type Cell Line Gene Regulation Microgravity Reference
Thyroid
Cancer 		FTC-133

  • Downregulation of VCL, PXN, ITGB1, RELA, ERK1, ERK2 in RPM-AD and MCS

  • Suppression of MIK67 and SRC in MCS

  • Upregulation of ICAM1, COL1A1, and IL6 in RPM-AD cells

 Spaceflight to the ISS,
5 d		 [182]
FTC-133

  • DEX inhibited dose-dependent spheroid formation;

  • NFKB2, VEGFA, CTGF, CAV1, BCL2 (L1), or SNAI1 were clearly affected by DEX.

 RPM,
4 h, 3 d		 [183]
FTC-133

  • Exosomal microRNA composition;

  • Array scan of a total of 754 miRNA targets: more than 100 differentially expressed miRNAs

 Spaceflight to the ISS,
12 d		 [184]
FTC-133
WRO
ML-1
Nthy-ori 3-1

  • DEGs MYC, NR3C1, FKBP5, DUSP1, MUC1, MAPK14

  • Balance between adhesion, anti-adhesion, and cell–cell connections enable detachment of adherent thyroid cells on the RPM

 RPM
3 d		 [185]
Breast cancer CRL2351

  • Upregulation of VIM, RHOA, BRCA1, and MAPK1 in AD and MCS

  • Upregulation of ERBB2 in MCS.

  • No significant change in VEGF and RAB27A.

 RPM,
5 d		 [186]
MCF-7

  • Significant upregulations of the mRNAs of enzymes degrading heme, ANXA1, ANXA2, CTGF, CAV2, ICAM1, FAS, Casp8, BAX, p53, CYC1 and PARP1 in MCS cells vs. 1g and AD cells.

 RPM,
24 h		 [187]
MCF-7, MDA-MB-231

  • MCF-7: Downregulation of FAK1, PXN, TLN1, VCL, and CDH1 in AD cells and PXN, TLN, and CDH1 in MCS. Vinculin and β-catenin are key mediators of MCS formation.

  • MDA-MB-231: No change in ACTB, TUBB, FN1, FAK1, and PXN gene expression.

  • Downregulation of LAMA3, ITGB1 mRNAs in AD cells, and ITGB1, TLN1, and VCL mRNAs in MCS.

 RPM,
24 h		 [188]
MCF-7

  • Early upregulation of KRT8, RDX, TIMP1, CXCL8 mRNAs

  • Downregulation of VCL after the first parabola.

 TEXUS-54,
6 min of r-µg, PFC,
31 parabolas		 [180]
MDA-MB-231

  • Upregulation of ICAM1, CD44 and ERK1 mRNAs after the first parabola (P1)

  • Delayed upregulation of NFKB1, NFKBIA, NFKBIB, and FAK1 after the last parabola (P31).

  • PRKCA, RAF1, and BAX mRNAs were not changed.

  • Cleaved caspase-3 was not detectable in MDA-MB-231 cells exposed to PF maneuvers.

 PFC,
31 parabolas		 [189]
MDA-MB-231

  • DEGs in MCS: AKT, KI67, BCL2, BAX, CD44, and MMP9 after 72h; AKT, KI67, BCL2, and MMP9 after 24 h

  • DEGs in RPM-AD: BAX, CD44, and MMP9 after 72 h; BCL2 and MMP9 after 24 h

 RPM
24 h, 72 h		 [190]
MCF-7, MDA-MB-231

  • qPCR-verified genes search in the mammalian phenotype database and the human genome-wide association studies (GWAS) Catalogue

  • ERK1, AKT1, MAPK14, EGFR, CTNNA1, CTNNB1, ITGB1, COL4A5, ACTB, and TUBB gene expression of MCSs differentially regulated in both cell types.

  • 7 genes (ACTB, CD44, EGFR, ITGB1, PXN, TUBB, and VCL) were successfully analyzed using WCGNA

 RPM
14 d		 [191]
Prostate
cancer 		PC-3

  • 3 d: Downregulation of VEGF, SRC1, AKT, MTOR, and COL1A1 in MCS.

  • No change in FLT1, RAF1, MEK1, ERK1, FAK1, RICTOR, ACTB, TUBB, and TLN1 mRNAs.

  • Upregulation of ERK2 and TLN1 in AD and FLK1, LAMA3, COL4A5, FN1, VCL, CDH1, and NGAL mRNAs in AD and MCS

  • 5 d: Downregulations of VEGF in AD and MCS, FN1, CDH1, and LAMA3 in AD and SCR1 in MCS.

  • Upregulations of FLT1, AKT, ERK1, ERK2, LCN2, COL1A1, TUBB, and VCL mRNAs in AD and MCS.

  • Upregulations of FLK1, FN1, and COL4A5 in MCS as well as LAMB2, CDH1, RAF1, MEK1, SRC1, and MTOR mRNAs in AD.

 RPM,
3 d, 5 d		 [192]
PC-3

  • 24 h: Upregulation of ACTB, MSN, COL1A1, LAMA3, FN1, TIMP1, FLT1, EGFR1, IL1A, IL6, CXCL8, and HIF1A in MCS.

  • Elevation of LAMA3, COL1A1, FN1, MMP9, VEGFA, IL6, and CXCL8 mRNAs in AD.

  • Downregulation of TUBB, KRT8, IL1B, IL7, PIK3CB, AKT1 and MTOR in AD.

 RPM,
30 min, 2 d, 4 d, and 24 h		 [193]
PC-3

  • Differentially expressed regulatory lncRNAs and micro RNAs, portfolio of 298 potential biomarkers.

  • NGS: 5 upregulated cytokines (CCL2, CXCL1, IL6, CXCL2, CCL20), one zinc-finger protein (TNFAIP3), and one glycoprotein (ICAM1).

  • Regulated miR-221 and the co-localized lncRNA MIR222HG induced by PF maneuvers.

 PFC,
31 parabolas		 [194]
Lung cancer A549, H1703

  • 24 h: A549 and H1703 highly expressed the migration-related genes MMP2, MMP9, TIMP1, and TIMP2 compared to CONT.

 3D clinostat,
24 h, 38 h		 [195]
CRL-5889

  • TP53, SOX2, CDKN2A, PTEN, and RB1 gene expressions were significantly upregulated in AD.

  • No change in AKT3, PIK3CA, and NFE2L2.

 RPM,
72 h		 [196]
A549

  • S-µg induced increased expression of FCGBP, BPIFB, F5, CST1, and CFB

  • Potential biomarkers for lung cancer

 2D clinostat 24 h, 48 h, 72 h [197]
Colorectal cancer DLD1 cells

  • Upregulation of PTEN and FOXO3

  • Downregulation of AKT

  • Increase in apoptosis

 RCCS-HARV [198]
Gastric
Cancer 		EPG85-257 RDB EPG85-257 P

  • Reduced expression of genes related to drug resistance and increased DNA/RNA damage marker expression

 RCCS,
72 h		 [199]
Liver cancer HepG2 cells
hBTSCs

  • Significant upregulation of

  • OCT4, SOX17, and ALB in HepG2 cells

 RCCS,
15 d		 [200]
Pancreas
Cancer 		PaCa-44

  • Metabolic reprogramming orchestrated by the activation of HIF-1α and PI3K/Akt pathways

 RPM,
1 d, 7 d, 9 d		 [201]
Skin cancer (Melanoma) BLM

  • Downregulation of the endothelial NOS-sGCMRP4/MRP5 pathway.

  • Suppression of sGC expression and activity correlates inversely to tumor aggressiveness.

  • Downregulation of cancer-related genes iNOS and GC-A/GC-B.

 Fast rotating
2D clinostat		 [202]

Abbreviations: Adherent (AD); days (d); dexamethasone (DEX); differentially expressed genes (DEGs); high aspect ratio vessels (HARV); hours (h); International Space Station (ISS); parabolic flight campaign (PFC); random positioning machine (RPM); real microgravity (r-µg); rotating cell culture system (RCCS); simulated microgravity (s-µg); Technologische EXperimente Unter Schwerelosigkeit (TEXUS); three-dimensional (3D); two-dimensional (2D).