Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.08.31.275065

Non-coding RNAs in fluid shear stress-driven and reactive oxygen species-mediated colon cancer metastasis

KrishnaPriya, S.·Banerjee, S.·Karunagaran, D.·Suraishkumar, G. K.
View original source ↗Export metadata ↓

Abstract

BackgroundColon adenocarcinoma (COAD) is the third most common cancer in the world. Fluid shear stress (FSS) and intracellular reactive oxygen species (ROS) levels are known to mediate COAD metastasis. The present work was performed to explore the role of regulatory non-coding RNA molecules associated with FSS and ROS in COAD metastasis. MethodsThe interactions between the mRNAs associated with FSS and ROS, the corresponding miRNAs, lncRNAs and circRNAs in COAD metastasis were used to generate the mRNA-miRNA-lncRNA-circRNA network. The expression levels of the RNAs in the network were also considered besides the identification of RNA hubs and modules. Further, functional enrichment and survival analysis of the significant miRNAs together with the OncoPrint as well as survival analysis of the selected mRNAs were performed. Subsequently, their functional role was also corroborated with existing literature. ResultsTen significant miRNA hubs were identified, out of which hsa-miR-17-5p and hsa-miR-20a-5p were found to interact with a lncRNA, CCAT2 and hsa-miR-335 was found to interact with four circRNAs. 60% of the FSS and ROS associated mRNAs and 90% of the top 10 miRNA-enriched pathways that emerged from the functional analysis were reported to be involved in COAD metastasis. 15 significant miRNAs were identified in ten different modules suggesting their importance in FSS and ROS mediated COAD metastasis. Finally, ten miRNAs and three mRNAs associated with FSS and/or ROS were identified as significant overall survival markers; 33 mRNAs were also identified as metastasis-free survival markers whereas 15 mRNAs showed >10% gene alterations in TCGA-COAD data and hence emerged as significant molecular markers in the process. ConclusionWe hypothesize that the biologically significant RNAs identified in this integrated analysis may provide valuable insights to understand the molecular mechanism of the FSS driven and ROS mediated COAD metastasis and to design efficient treatment strategies.

Explore related subjects

systems biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

KrishnaPriya, S., Banerjee, S., Karunagaran, D., Suraishkumar, G. K.. 2020-08-31. Non-coding RNAs in fluid shear stress-driven and reactive oxygen species-mediated colon cancer metastasis. https://doi.org/10.1101/2020.08.31.275065

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Homogeneous network inference for subtype-stratified master regulator analysis in cancer

Master-regulator analysis of 34 TCGA tumour cohorts (cancer x molecular subtype; n between 27 and 562 tumours) requires one regulatory network per cohort. Mutual-information (MI) networks inferred with ARACNe3 are the usual choice, but they are not available for the smallest cohorts; filling the gap with correlation networks would mix two methods inside the very comparison between subtypes that the analysis is meant to make. We therefore infer every network with a single procedure, fixed-size Spearman regulons (FSR): rank correlation between regulator and target, a fixed effect-size threshold rho >= 0.2, the per-target data-processing-inequality (DPI) pruning implemented in corto, bootstrap support, and truncation to the 100 best-supported targets per regulator. We quantify what this choice concedes and what it provides, labelling each claim as a standard result, a heuristic, or an empirical result. Rank correlation is more powerful than the MI estimators we simulated for n < 200 but cannot see non-monotone dependence, which in a synthetic worst case costs at most about 0.05-0.10 of the master regulators recovered; the per-target DPI is a heuristic with a measurable disagreement rate with the MI-based one; and pairwise dependence is not direct interaction, for MI and correlation alike. Where both methods are feasible (n >= 95) they overlap in 0.7 of the top-20 regulators, the same as two filterings of the same ARACNe3 network, although the rank correlation of the full score vector shows a measurable method effect in the tail. Subsampling large real cohorts indicates that networks inferred from fewer than 60 tumours do not reliably reproduce their own cohort's master regulators, that 60-100 is a grey zone, and that a cancer-wide network does not rescue small subtypes. We present FSR as an adequate and uniform choice for multi-cohort analysis, not as a statistically superior one.

systems biology↗
bioRxiv2026

Low-fidelity simulator selection for multi-fidelity inference of epithelial vertex models

Vertex models link cell division, neighbour exchange, and intercellular forces to epithelial tissue form through parameters such as junctional line tension and perimeter contractility. Bayesian inference of these parameters from data quantifies their uncertainty, but for stochastic models of proliferating tissues it requires many costly simulations. Multi-fidelity simulation-based inference reduces this cost by training on many runs of a cheaper, less accurate ('low-fidelity') simulator before refining with a few full ('high-fidelity') runs. Low-fidelity versions can be constructed in several ways, for example by stopping simulations early, coarsening the timestep, or averaging fewer replicates, but it is unclear which to choose before committing to costly training. To address this, we introduce PRISM (Paired Ranking Index for Simulator Matching), a screen that compares each candidate with the full simulator on paired runs, scoring agreement in cell-packing statistics against cost. For a vertex model of a proliferating tissue, PRISM flags stopping early as unreliable before training; once trained, this choice can produce confidently wrong parameter estimates. By contrast, a coarser timestep, within the range tested, is cheap and accurate; while fewer replicates are accurate but too costly. Using a screened low-fidelity simulator, multi-fidelity inference outperforms approximate Bayesian computation and neural-network inference trained on full simulations alone, at matched cost and with well-calibrated uncertainty. The same pattern recurs for a second vertex model fitted to published Drosophila pupal-wing imaging data, although there stopping halfway proves safe. Together, our findings suggest that which approximations are safe depends on the model, and that screening them before training makes multi-fidelity inference of tissue mechanics practical.

systems biology↗
bioRxiv2026

Calibrating developmental dynamics from single-cell atlases: lineage paths outrun least-action routes

Single-cell atlases infer developmental dynamics from destructive snapshots, yet how far realized lineage paths depart from such inferred dynamics has never been measured with controls. We introduce LADD (Least-Action Developmental Dynamics), a measurement framework that learns a stochastic developmental vector field from time-series single-cell RNA-seq and computes minimum-action and minimum-time paths, together with a three-layer calibration protocol that separates genuine path deviation from the generic cost of centroid measurement, and we compare its forecasting component with optimal-transport and flow-matching methods. In the lineage-resolved Caenorhabditis elegans atlas, the raw action ratio of observed lineage-centroid trajectories to optimal paths is 3.79, yet forward-simulated ensembles of the learned model itself score 2.07, leaving a genuine excess of about two-fold. In zebrafish (Danio rerio), the observed ratio sits entirely at the model's floor. Three mechanisms that could explain the residual deviation (detours, flow-opposition, and fate-map complexity) are each excluded; what remains is speed, with lineages moving 30-43% faster along the learned flow. We report validity boundaries for temporal resolution, cross-species comparison, and energetic interpretation, delimiting where action-based trajectory comparisons are meaningful.

systems biology↗