MIR375

Summary

MIR375 (microRNA 375, HGNC:31868) is a microRNA gene on chromosome 2q35.

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 494324 — 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:31868
Approved symbol	MIR375
Name	microRNA 375
Location	2q35
Locus type	RNA, micro
Status	Approved
Aliases	hsa-mir-375
Ensembl gene	ENSG00000198973
Ensembl biotype	miRNA
OMIM	611173
Entrez	494324
RNAcentral	URS000075BCF9 — miRNA, 64 nt, 54 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000362103

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000362103 — 1 exons

Exon	Start	End
ENSE00001436866	219001645	219001708

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 82.44.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	82.44	gold quality
blood	UBERON:0000178	74.93	gold quality
right frontal lobe	UBERON:0002810	74.29	gold quality
monocyte	CL:0000576	71.39	gold quality
placenta	UBERON:0001987	70.03	gold quality
stomach	UBERON:0000945	68.81	gold quality
omental fat pad	UBERON:0010414	68.58	gold quality
muscle layer of sigmoid colon	UBERON:0035805	67.15	gold quality
transverse colon	UBERON:0001157	64.89	gold quality
right lobe of thyroid gland	UBERON:0001119	64.22	gold quality
thyroid gland	UBERON:0002046	64.20	gold quality
minor salivary gland	UBERON:0001830	62.84	gold quality
skin of leg	UBERON:0001511	62.56	gold quality
body of stomach	UBERON:0001161	62.48	gold quality
pituitary gland	UBERON:0000007	62.12	gold quality
prostate gland	UBERON:0002367	58.14	gold quality
adenohypophysis	UBERON:0002196	57.33	gold quality
thoracic mammary gland	UBERON:0005200	55.70	gold quality
testis	UBERON:0000473	49.08	gold quality
left testis	UBERON:0004533	49.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, CTCF, ESR1, HNF1A, TCF3

Literature-anchored findings (GeneRIF, showing 40)

• miR-375 is an important regulator of YAP oncogene playing the role in hepatocellular carcinoma development. (PMID:20226166)
• Data show that up-regulated microRNA-375 is associated with type 2 diabetes and pancreatic islet amyloid formation and beta-cell deficit. (PMID:20467341)
• miR-375 may function as a tumor suppressor to regulate gastric cancer cell proliferation potentially by targeting the JAK2 oncogene, implicating a role of miR-375 in the pathogenesis of gastric cancer (PMID:20548334)
• Data show that inhibiting miR-375 in ERalpha-positive MCF-7 cells resulted in reduced ERalpha activation and cell proliferation. (PMID:20978187)
• Results indicate that the combination of hsa-miR-375 and hsa-miR-142-5p as a predictor of disease progression has the potential to predict recurrence risk for gastric cancer patients. (PMID:21343377)
• miR-375 is frequently down-regulated in esophageal cancer and is a negative regulator of PDK1. (PMID:21533613)
• The reduced levels of Sec23A protein were inversely correlated to the increased amount of miR-375 in the LNCaP and DU145 CaP cell lines when compared with normal prostate fibroblasts. (PMID:21593139)
• Low miR-375 is associated with esophageal squamous cell carcinoma. (PMID:21673684)
• Ectopic expression of miR-375 inhibited melanoma cell proliferation, invasion, and cell motility, and induced cell shape changes, strongly suggesting that miR-375 may have an important function in the development and progression of human melanomas (PMID:21723283)
• Data show that AEG-1/MTDH was directly regulated by miR-375. (PMID:21753766)
• MicroRNA-375 has a tumour-suppressive effect by inhibiting expression of IGF1R. Downregulation of microRNA-375, mainly through promoter methylation, is one of the molecular mechanisms involved in the development of oesophageal squamous cell carcinoma. (PMID:21813472)
• miR-375 is a key downstream effector of ASH1 function in lung cancer cells; the transcriptional coactivator YAP1 was determined to be a direct target of miR-375 (PMID:21856745)
• Increased expression of hsa-miR-375 resulted in loss of cellular organization and acquisition of a hyperplastic phenotype in a 3D culture model of mammary acinar morphogenesis. (PMID:21953071)
• Data show that MiR-375 expression was significantly reduced, and conversely, metadherin (MTDH) was significantly increased in nasopharyngeal carcinoma (NPC) samples. (PMID:22031094)
• miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo (PMID:22056881)
• Dual-luciferase assays showed that ASCL1 activated the expression of miR-375 by binding to the three E-box elements in the miR-375 promoter. These results imply a role of ASCL1 in SCLC via the upregulation of miR-375. (PMID:22172490)
• we propose miR-31 and -375 as novel candidate microRNAs specifically associated with early- and late-stage malignant progression, respectively, in Barrett’s esophagus. (PMID:22302717)
• miR-375 may be involved in the carcinogenesis of colorectal cancers and may be a potential biomarker for colorectal cancers. (PMID:22377847)
• miR-378, miR-375, miR-422a and miR-215 play an important role in the colorectal cancer as tumour suppressors (PMID:22469014)
• Re-expression of miR-375 was sufficient to sensitize TamR cells to tamoxifen and partly reversed EMT (PMID:22508479)
• Circulating miR-21 and miR-375 could be reliable prognostic markers for ESCC. These plasma markers might facilitate clinical decision-making to select prospective candidates, which need meticulous follow-up (PMID:22519435)
• results indicate that histone deacetylase inhibitors upregulate miRNAs, at least some of which act as tumor suppressors. lactate dehydrogenase B, which is regulated by the tumor suppressive miR-375, may therefore act as an oncogene in esophageal squamous cell carcinoma. (PMID:22752059)
• Functional roles of candidate genes EYA2 (20q13) and hsa-miR-375 (2q35) were studied by siRNA-mediated knock-down and overexpression, respectively, in hrHPV-containing cell lines. (PMID:22987659)
• downregulation of miR-375 expression in human gliomas may play an inhibitory role during the tumor development. (PMID:23103713)
• Decreased miR-375 correlated significantly with advanced disease stage and lymphatic metastasis in nonsmall cell lung cancer. (PMID:23206448)
• mir375 was downregulated in laryngeal squamous cell carcinoma. (PMID:23259291)
• miR-375 downregulation has a role in prognosis of esophageal squamous cell carcinoma (PMID:23301089)
• Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA-mRNA interactions. (PMID:23552692)
• results demonstrate that plasma levels of selected miRNAs are potential biomarkers to differentiate localized PCa and mCRPC. (PMID:23574937)
• Overexpression of miR-375 impacts cell proliferation, cell cycle distribution, and apoptosis of pancreatic cancer cells, miR-375 may play an important role in the novel therapeutic strategy for pancreatic cancer (PMID:23581226)
• low miR-375 expression was significantly associated with late stage disease, larger tumour size and the non-cohesive type of pattern of invasion in oral squamous cell carcinoma (PMID:23651447)
• MiR-375 and miR-10a were overexpressed in medullary thyroid carcinoma. (PMID:23685355)
• Mir-375 can enhance Rawq01 (ruthenium compound) induced cell death in human ovarian cancer both in vitro and in vivo. (PMID:23696927)
• study found that paclitaxel may induce an acquired drug resistance in cervical cancer, that is, paclitaxel upregulates miR-375 expression and overexpressed miR-375 consequently produces chemo-resistance in cervical cancer in vitro and in vivo (PMID:23778521)
• MiR-375 targets p53 in cancer cells to regulate the response to ionizing radiation and etoposide treatment. (PMID:23835407)
• The upregulation of miR-375 may be one of the molecular mechanisms involved in the development and progression of pediatric acute myeloid leukemia. (PMID:23864342)
• miR-375-induced hEBs have similar characteristics to those of mature islets. (PMID:23897763)
• Antagonising miR-375 may enhance the effects of exendin-4 in patients, and controlling the expression of miR-375 could assist mature hESCs-derived beta-cells (PMID:24120394)
• this review summarizes the present understanding of the tumor suppressive role of miR-375 in cancer progression; the mechanisms underlying the dysregulation of miR-375; the potential use of miR-375 in prognosis and diagnosis and the therapeutic prospects of miR-375 in cancer. (PMID:24166096)
• the negative correlation between Androgen receptor and total DNA methyltransferase activity is one of mechanisms to influence the methylation status of miR-375 promoter, which in turn regulates the expression of miR-375. (PMID:24173286)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dre-mir-375-2	ENSDARG00000080708
danio_rerio	dre-mir-375-1	ENSDARG00000081499
mus_musculus	Mir375	ENSMUSG00000065616
drosophila_melanogaster	mir-375	FBGN0262177

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.