ATC‑SpecIfIc TP53 ProfIlIng: mIcro RNA Interactıons & Mutatıons
ATC‑SpecIfIc TP53 ProfIlIng: mIcro RNA Interactıons & Mutatıons
This web‑based tool is designed to examine—at high resolution—the 3′‑UTR region of the TP53 gene, which plays a critical role in aggressive tumors such as anaplastic thyroid cancer (ATC). TP53 serves as the “central command” for cellular stress responses and tumor‑suppression mechanisms; therefore, even small alterations within its 3′‑UTR can dramatically affect TP53 protein levels.
Why the 3′‑UTR?
Post‑transcriptional control hub: miRNAs bind to the 3′‑UTR to regulate TP53 mRNA stability and translational efficiency.
The “hidden” impact of somatic mutations: Single‑nucleotide changes that disrupt miRNA binding—without touching the coding region—can disable the gene’s tumor‑suppressor function.
Value Added by the Tool
Full‑length alignment: The patient‑specific 3′‑UTR sequence supplied by the user is aligned nucleotide‑by‑nucleotide to the reference TP53 sequence, capturing single‑nucleotide variants (SNVs) and small indels comprehensively.
miRNA seed overlap detection: The embedded MIRNA_CSV list contains the seed positions of ~100 miRNAs that are experimentally validated or predicted to bind TP53. The tool detects in real time whether any mutation intersects these seed windows.
Pre‑computed miRES score: Calculated as the product of binding strength (B), functional impact (F), pathogenicity linkage (P) and conservation (C). Thus, even before a mutation‑specific recalculation, interactions are already ranked by their clinical relevance.
Fast and platform‑agnostic: All computations run client‑side in JavaScript—no server load, high privacy.
Research‑to‑clinic bridge:
Scientist: Instantly receives a summary table to hypothesize mutation‑miRNA relationships.
Molecular pathology lab: Rapidly selects which miRNAs will proceed to functional testing.
Clinician: Can incorporate potential prognostic/predictive biomarkers into the report.
Mandatory Criteria for the Patient TP53 3′‑UTR Sequence You Paste into the Tool
Full‑length match
• Reference sequence (REF_SEQ) length = 1188 nucleotides.
• The patient sequence must also be exactly 1188 nt; even a single extra or missing base will trigger a “Length mismatch!” error.
DNA letters only (A T G C)
• The RNA symbol U and the ambiguous base N are not accepted.
• Case‑insensitive—the tool converts everything to uppercase.
Spaces and line breaks allowed; numbers & symbols forbidden
• Multi‑line FASTA blocks, tabs, and other whitespace are automatically stripped.
• Digits (1, 2, 3 …), punctuation (., ;), emojis, etc. are removed; otherwise they can cause a length error.
Optional FASTA header
• You may add a header such as “>Sample_007” on the first line; the code ignores it.
• Whether or not you include a header, you must paste only one sequence.
One sequence, one patient
• Do not paste multiple sequences in the same box—the analysis will consider only the first 1188 nt.
DNA format ≠ cDNA
• Provide the genomic TP53 3′‑UTR; do not include introns, promoter, coding region, or a poly‑A tail.
Pre‑check recommendation
• Before pasting, count the sequence length in a text editor (Notepad++ → “Length” indicator).
• If the GC‑content is not ~50 %, you may have copied the reference from the wrong location.
Binding Strength ( B ) : Indicates how strongly a miRNA binds to its target site in the TP53 3′-UTR.
The binding energy (ΔG) or binding score produced by algorithms such as RNAhybrid, TargetScan, and similar tools is used.
The ΔG value is normalized on a relative scale
Functional Impact ( F ) : The miRNA’s direct or indirect ability to repress or support TP53.
A five-level categorical system is used, based on literature and experimental data:
1. Direct OG - miRNA has been shown to directly repress TP53 expression - 1.0
2. Indirect OG - miRNA has been shown to suppress TP53 pathways indirectly (e.g., by activating MDM2) - 0.85
3. Unclear / Predicted - Functional effect unknown; only in silico evidence available - 0.70
4. Indirect TS - miRNA has been shown to support TP53 pathways indirectly (e.g., via PTEN, ATM) - 0.60
5. Direct TS - miRNA has been shown to directly increase TP53 expression - 0.50
Pathogenicity Link ( P ) : The strength of the miRNA’s association with ATC, thyroid cancers, or cancer in general.
1. ATC (Anaplastic Thyroid Cancer) + OG - 2.0
2. ATC + TS - 0.001
3. Thyroid cancer + OG - 1.5
4. Thyroid cancer + TS - 0.01
5. INSUFFICIENT EXPERIMENTAL EVIDENCE - 0.5
For this type of miRNA, the following experimental evidence is not available in the current literature:
qRT-PCR / Northern blot (expression level analysis)
Functional cell culture assays (proliferation, apoptosis, migration/invasion, colony formation)
Luciferase reporter assay (target gene validation)
Western blot / qRT-PCR (target gene/protein expression analysis)
Rescue experiments (reversal of effect via target gene manipulation)
Animal models (in vivo) (tumor growth/metastasis function)
Immunohistochemistry (IHC) (tissue-level protein validation)
Therefore, there is no functional or clinical role experimentally demonstrated for this miRNA. Only sequence/database registration or in silico predictions are available.
6. General cancer + OG - 1.0
7. General cancer + TS - 0.1
Conservation Score ( C ) : Indicates how conserved the miRNA target region is across different species.
The PhyloP genomic conservation score is used.
C is the normalized (0.1 - 0.6) mean PhyloP value of all bases within the target region.