MIR99A

Summary

MIR99A (microRNA 99a, HGNC:31650) is a microRNA gene on chromosome 21q21.1.

microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop.

Source: NCBI Gene 407055 — RefSeq curated summary.

At a glance

• Gene type: non-coding (miRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31650
Approved symbol	MIR99A
Name	microRNA 99a
Location	21q21.1
Locus type	RNA, micro
Status	Approved
Aliases	hsa-mir-99a
Ensembl gene	ENSG00000207638
Ensembl biotype	miRNA
OMIM	614509
Entrez	407055
RNAcentral	URS0000208A34 — miRNA, 81 nt, 24 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000384906

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000384906 — 1 exons

Exon	Start	End
ENSE00001499913	16539089	16539169

Expression profiles

Bgee: expression breadth broad, 64 present calls, max score 91.30.

Top tissues by expression

64 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
midbrain	UBERON:0001891	91.30	gold quality
epididymis	UBERON:0001301	87.93	gold quality
kidney	UBERON:0002113	85.82	gold quality
calcaneal tendon	UBERON:0003701	85.77	gold quality
stomach	UBERON:0000945	84.78	gold quality
islet of Langerhans	UBERON:0000006	83.29	gold quality
blood	UBERON:0000178	82.14	gold quality
adrenal tissue	UBERON:0018303	81.67	gold quality
heart	UBERON:0000948	79.82	gold quality
intestine	UBERON:0000160	78.42	gold quality
right atrium auricular region	UBERON:0006631	77.65	gold quality
placenta	UBERON:0001987	77.20	gold quality
lung	UBERON:0002048	77.06	gold quality
liver	UBERON:0002107	76.99	gold quality
monocyte	CL:0000576	75.35	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	73.80	gold quality
colon	UBERON:0001155	72.95	gold quality
right adrenal gland	UBERON:0001233	72.30	gold quality
smooth muscle tissue	UBERON:0001135	72.29	gold quality
anterior cingulate cortex	UBERON:0009835	69.20	gold quality
omental fat pad	UBERON:0010414	68.24	gold quality
endometrium	UBERON:0001295	66.96	gold quality
tibial nerve	UBERON:0001323	66.34	gold quality
skin of abdomen	UBERON:0001416	65.89	gold quality
heart left ventricle	UBERON:0002084	65.86	gold quality
zone of skin	UBERON:0000014	65.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	64.55	gold quality
esophagus mucosa	UBERON:0002469	64.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	64.25	gold quality
ascending aorta	UBERON:0001496	64.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.32

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• 3 targets of miR-99 family (miR-99a, -99b, -100) were SMARCA5, SMARCD1, mTOR; PSA is regulated by miR-99 family, at least partially, by repression of SMARCA5; suggests key functions and targets of miR-99 family in prostate cancer suppression and prognosis (PMID:21212412)
• Findings suggest that the miR-99a-mTOR/FGFR3 pathway is crucial for controlling tumor growth in a wide range of human cancers that harbor upregulation of the Src-related oncogenic pathways. (PMID:21383697)
• miR-99a is one of the regulators of the IGF-1R signaling pathway in keratinocytes (PMID:21687694)
• Data show that Differentially expressed miRNAs including miR-99a, miR-100, miR-125b, miR-192, and miR-429 were detected in pancreatic cancer stem cells. (PMID:21785383)
• miR-99a suppresses HCC growth by inducing cell cycle arrest, suggesting miR-99a as potential tumor suppressor for HCC therapeutics. (PMID:21878637)
• members of the oncomir miR-17-92 cluster were upregulated, but themiR-125b/miR-99a/let-7c, miR-106b/miR-93/miR-25 and miR-212/miR-132 clusters are also coordinately regulated either by stromal cell contact alone or by CD154 (PMID:22024720)
• Explored deregulation of miRNAs targeting mTOR kinase (miR-99a, miR-100 and miR-199b) in endometrioid endometrial carcinoma. mTOR kinase expression was increased in EEC tissues and was accompanied by decreased expression of all three miRNAs. (PMID:22920721)
• Results indicate that MTOR is a direct target of miR-99a. (PMID:23173671)
• results indicated that miR-99a and miR-100 inhibited cell proliferation by suppressing mTOR in esophageal squamous cell carcinoma cell lines (PMID:23292834)
• discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3’-UTR of FGFR3, blocking gene regulation of miR-99a. (PMID:23298836)
• down regulation of fibroblast growth factor receptor 3 (FGFR3) and PI3K/Akt signaling mechanisms leading to inhibition of cell proliferation and induction of molecular mechanisms of apoptosis (PMID:23409016)
• Expression of a microRNA-resistant form of IGF1R protects these cells from inhibition by the miR-99a/let7c/125b-2 cluster (PMID:23503464)
• members of miR-99 family (miR-99a, miR-99b, miR-100) were expressed during dermal wound healing. (PMID:23724047)
• miR-99a repressed oral cancer cell migration and invasion partly through decreasing MTMR3 expression (PMID:23731011)
• miR-99a functions as a tumor suppressor by targeting mTOR. (PMID:23893385)
• MiR-125b, miR-100 and miR-99a co-regulate vincristine resistance in childhood acute lymphoblastic leukemia. (PMID:23915977)
• MiR-100 and miR-99a have critical roles in altering cellular processes by targeting both the FKBP51 and IGF1R/mTOR signalling pathways in ALL. (PMID:24030073)
• miR-99a functions as a tumor metastasis suppressor in Oral squamous cell carcinoma cells and mutually regulates IGF1R expression in a reciprocal regulation (PMID:24410957)
• miR-99a expression was remarkably downregulated in serums, tissues and cell and suppresses epithelial ovarian cancer cell proliferation by targeting FGFR3. (PMID:24456664)
• The MiR-99a/Let-7c/miR-125b signature may improve the selection of patients with KRAS wild-type metastatic colorectal cancer as good candidates for anti-EGFR therapy. (PMID:24503111)
• miR-99a antitumor activity is achieved by targeting the mTOR/p-4E-BP1/p-S6K1 pathway in human breast cancer cells. (PMID:24637915)
• Low miR-99a expression is associated with cervical cancer. (PMID:24668416)
• ANRIL-mediated growth promotion is in part due to epigenetic repression of miR-99a/miR-449a in gastric cancer (PMID:24810364)
• Our data indicated that miR-99a might act as a tumor suppressor in bladder cancer and was significantly down-regulated in development of bladder cancer. (PMID:24957100)
• miR-99a/mTOR pathway was involved in diaporine A-induced tumor suppression in non-small cell lung cancer cells. (PMID:25046358)
• Authors have identified microRNAs-99a/100 mediate a direct relationship between FGFR3 and FOXA1 and potentially facilitate cross talk between these pathways in UCC. (PMID:25071007)
• Data indicate that proto-oncogene c-Akt (AKT1) is directly involved in miR-99a-mediated tumor suppression. (PMID:25187230)
• Results show that overexpression of miR-107 and miR-99a-3p were significantly associated with improved progression-free and/or overall survival. (PMID:25197016)
• Overexpression of miR-99a suppressed expression of mTOR and its downstream gene, HIF-1alpha. (PMID:25348507)
• MiR99a reduced cell proliferation, colony formation ability, migration and invasion through regulation of FGFR3 in prostate cancer. (PMID:25352177)
• The co-expression of miR-125b and miR-99a contributed to the vincristine resistance to childhood acute megakaryoblastic leukemia cells due to actively transcribed miR99a/miR-125b locus on chromosome 21q21.1. (PMID:25571789)
• The mir-99a approximately 125b cluster might be a novel target for multiple myeloma treatment. (PMID:25826415)
• Data show that microRNA MiR-99a, which was down-regulated in cancerous tissues, was significantly increased in plasma after operation. (PMID:25950115)
• High MIR 99a is associated with muscle-invasive bladder cancer. (PMID:25990459)
• miR-99a regulates CTDSPL, which induces the G1/S transition by increasing Cyclin expression and play a significant role in proliferation of CB-MKs. (PMID:26055579)
• MiR-99a functions as a tumor suppressor. (PMID:26163618)
• MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in breast cancer cells. (PMID:26417931)
• Data show that the let-7c/miR-99a/miR-125b cluster controlled tumorigenesis by targeting IL-6, IL-6R and IGF1R. (PMID:26455324)
• miR-99a directly regulates the invasion and migration in lung adenocarcinoma by targeting NOX4. (PMID:26986073)
• we have demonstrated that low expression of miR-99a and miR-100 is present in cell populations which are relatively radiation insensitive, for example in prostate cancer stem cells and in castration-resistant prostate cancer. (PMID:27340920)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dre-mir-99-2	ENSDARG00000081315
danio_rerio	dre-mir-99-1	ENSDARG00000082197
mus_musculus	Mir99a	ENSMUSG00000065530
rattus_norvegicus	Mir99a	ENSRNOG00000035524

Paralogs (7): MIR99B (ENSG00000207550), MIR10B (ENSG00000207744), MIR125B2 (ENSG00000207863), MIR125B1 (ENSG00000207971), MIR100 (ENSG00000207994), MIR125A (ENSG00000208008), MIR10A (ENSG00000284038)

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.