MiR-324-5p

Last updated

miR-324-5p is a microRNA that functions in cell growth, apoptosis, cancer, [1] epilepsy, [2] [3] neuronal differentiation, [4] psychiatric conditions, [5] cardiac disease pathology, [6] [1] and more. [7] As a microRNA, it regulates gene expression through targeting mRNAs. Additionally, miR-324-5p is both an intracellular miRNA, meaning it is commonly found within the microenvironment of the cell, and one of several circulating miRNAs found throughout the body. [8] Its presence throughout the body both within and external to cells may contribute to miR-324-5p's wide array of functions and role in numerous disease pathologies – especially cancer – in various organ systems.

Contents

History

miR-324-5p first appeared in literature in a paper published by John Kim et al. in early 2004 that identified 32 entirely new miRNAs from cultured rat cortical neurons using miRNA cloning and RNA analysis. [9] The miRNA quickly gained traction in scientific literature, appearing in articles about the evolutionary conservation of microRNAs, [10] HIV, [11] cancer, [12] and other topics within a few years. Today, the functions and roles of miR-324-5p are still not yet fully characterized. [13]

Structure and targets

miR-324-5p is a reverse strand miRNA, meaning it is produced from the 5' end of the associated RNA, and spans from position 7,223,342 to 7,223,364 on chromosome 17. [14] Its sequence is CGCAUCCCCUAGGGCAUUGGUG. [15] [16]

miRNA forms following cleavage of pre-miRNA at the hairpin loop by the enzyme dicer within the cytosol. Interestingly, both strands of miR-324's pre-miRNA hairpin loop structure, miR-324-5p and miR-324-3p, become active miRNAs with distinct targets and functions. [17] miR-324-5p has between 166 and 469 predicted targets, [18] [19] [14] including regulators of cell growth, proliferation, survival, cytoskeletal structure, ATP transport, and ion channels. [18] Though miR-324-5p is found on chromosome 17, its targets span across all chromosomes. [16]

Functions

Cell growth and survival

miR-324-5p likely regulates cell growth and survival through interaction with multiple pathways. Published research demonstrates that this miRNA interacts with the Hedgehog (HH) signaling pathway via interactions with HH transcription factor Gli1 [20] and HH protein receptor Smo, [21] often contributing to tumorigenesis. miR-324-5p's activating interaction with the protein NfkB also regulates numerous components of cell survival, including cell cycle control, enzyme synthesis, and cell adhesion. [22] In addition, miR-324-5p regulates components of the MAPK pathway, influencing cell growth, proliferation, and survival. Specifically, miR-324-5p downregulates RAF and ERK and is necessary for normal levels of cell growth. Reduced expression leads to increased cell growth and proliferation, and overexpression limits growth, leading to its role in oncogenesis. [23]

miRNA-324-5p targets multiple oncogenes, contributing to both tumorigenesis and tumor suppression in different cancers. Role of miRNA in a cancer cell.svg
miRNA-324-5p targets multiple oncogenes, contributing to both tumorigenesis and tumor suppression in different cancers.

Cancer

Both up and downregulation of miR-324-5p is shown to contribute to various types of cancer. [17]

miR-324-5p plays a role in inflammation and tumorigenesis in colorectal cancer through regulation of CUEDC2, which regulates inflammation via interaction with NF-kB signaling. [12] miR-324-5p can inhibit glioma proliferation, [20] suppress hepatocellular carcinoma and nasopharyngeal carcinoma cell invasion, [24] [25] and regulate growth and pathology in multiple myeloma. [26] Additionally, chromosome 17 deletions, which include deletion of miR-324-5p, are present in 10% of multiple myeloma patients and are associated with poorer prognosis. [26]

In contrast, overexpression of miR-324-5p in gastric cancer cells reduces cell death and promotes growth and proliferation. [27] miR-324-5p has also been shown to reduce the viability of gastric cancer cells via downregulation of TSPAN8, and miR-324-5p expression increased apoptosis in these same gastric cancer cells. [28]

Epilepsy

Seizures are characterized by high levels of synchronized neuronal activity. One important regulator of neuronal activity is the hyperpolarizing A-type current mediated by potassium channel KV4.2. [29] miR-324-5p downregulates KV4.2, exacerbating conditions that lead to seizure onset, and downregulation of miR-324-5p in mouse models of epilepsy is seizure-suppressive. [3]

Changes in miRNA expression are seen in epileptogenesis and in other disease pathologies. [30] [31] In epilepsy, miR-324-5p expression has been shown to increase [32] and decrease [33] at different timepoints and loci.

Importantly, miR-324-5p has increased association with the RISC complex following seizure in mice, indicating more suppressive activity. [3] [34]

Overall, this suggests that miR-324-5p plays a role in epileptogenesis via targeting of potassium channel KV4.2.

Cardiac disease

miR-324-5p contributes to cardiac disease pathophysiology and cardiomyocite death through translational inhibition of Mtfr1, leading to reduced mitochondrial fission, apoptosis, and myocardial infarction. [6]

Psychiatric conditions

MiRNA expression profiles are altered in psychiatric conditions, including depression, [5] anxiety, [35] and PTSD. [36] It has been demonstrated that miR-324-5p expression is altered in the brains of suicide victims with depression [5] and in the amygdala, the fear center of the brain, in PTSD. [36] MiRNAs are an underexplored potential biomarker and target for treatment for psychiatric disease. [37]

Future research and potential in medicine

miRNA-324-5p is a relatively new and understudied microRNA. It is an important regulator in several diseases, and its effects span across the body from neuronal dysregulation in seizure to hepatocellular carcinoma and cardiac disease. Because microRNAs have numerous targets, they are capable of regulating multiple pathways and circuits, an ability that may be useful in the treatment of complex disorders like epilepsy in which many subsystems are dysregulated. However, the wide-ranging functions of miRNAs may be limiting as well. microRNA expression modulation could lead to unanticipated physiological effects and not provide adequate specificity. [38]

Related Research Articles

mir-9/mir-79 microRNA precursor family

The miR-9 microRNA, is a short non-coding RNA gene involved in gene regulation. The mature ~21nt miRNAs are processed from hairpin precursor sequences by the Dicer enzyme. The dominant mature miRNA sequence is processed from the 5' arm of the mir-9 precursor, and from the 3' arm of the mir-79 precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In vertebrates, miR-9 is highly expressed in the brain, and is suggested to regulate neuronal differentiation. A number of specific targets of miR-9 have been proposed, including the transcription factor REST and its partner CoREST.

mir-124 microRNA precursor family

The miR-124 microRNA precursor is a small non-coding RNA molecule that has been identified in flies, nematode worms, mouse and human. The mature ~21 nucleotide microRNAs are processed from hairpin precursor sequences by the Dicer enzyme, and in this case originates from the 3' arm. miR-124 has been found to be the most abundant microRNA expressed in neuronal cells. Experiments to alter expression of miR-124 in neural cells did not appear to affect differentiation. However these results are controversial since other reports have described a role for miR-124 during neuronal differentiation.

mir-129 microRNA precursor family

The miR-129 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. This microRNA was first experimentally characterised in mouse and homologues have since been discovered in several other species, such as humans, rats and zebrafish. The mature sequence is excised by the Dicer enzyme from the 5' arm of the hairpin. It was elucidated by Calin et al. that miR-129-1 is located in a fragile site region of the human genome near a specific site, FRA7H in chromosome 7q32, which is a site commonly deleted in many cancers. miR-129-2 is located in 11p11.2.

mir-17 microRNA precursor family

The miR-17 microRNA precursor family are a group of related small non-coding RNA genes called microRNAs that regulate gene expression. The microRNA precursor miR-17 family, includes miR-20a/b, miR-93, and miR-106a/b. With the exception of miR-93, these microRNAs are produced from several microRNA gene clusters, which apparently arose from a series of ancient evolutionary genetic duplication events, and also include members of the miR-19, and miR-25 families. These clusters are transcribed as long non-coding RNA transcripts that are processed to form ~70 nucleotide microRNA precursors, that are subsequently processed by the Dicer enzyme to give a ~22 nucleotide products. The mature microRNA products are thought to regulate expression levels of other genes through complementarity to the 3' UTR of specific target messenger RNA.

mir-1 microRNA precursor family

The miR-1 microRNA precursor is a small micro RNA that regulates its target protein's expression in the cell. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give products at ~22 nucleotides. In this case the mature sequence comes from the 3' arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In humans there are two distinct microRNAs that share an identical mature sequence, and these are called miR-1-1 and miR-1-2.

The miR-34 microRNA precursor family are non-coding RNA molecules that, in mammals, give rise to three major mature miRNAs. The miR-34 family members were discovered computationally and later verified experimentally. The precursor miRNA stem-loop is processed in the cytoplasm of the cell, with the predominant miR-34 mature sequence excised from the 5' arm of the hairpin.

mIRN21 Non-coding RNA in the species Homo sapiens

microRNA 21 also known as hsa-mir-21 or miRNA21 is a mammalian microRNA that is encoded by the MIR21 gene.

An oncomir is a microRNA (miRNA) that is associated with cancer. MicroRNAs are short RNA molecules about 22 nucleotides in length. Essentially, miRNAs specifically target certain messenger RNAs (mRNAs) to prevent them from coding for a specific protein. The dysregulation of certain microRNAs (oncomirs) has been associated with specific cancer forming (oncogenic) events. Many different oncomirs have been identified in numerous types of human cancers.

miR-155 Non-coding RNA in the species Homo sapiens

MiR-155 is a microRNA that in humans is encoded by the MIR155 host gene or MIR155HG. MiR-155 plays a role in various physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and enhance the progression of cardiovascular diseases.

mir-126

In molecular biology mir-126 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several pre- and post-transcription mechanisms.

miR-137

In molecular biology, miR-137 is a short non-coding RNA molecule that functions to regulate the expression levels of other genes by various mechanisms. miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types including colorectal cancer, squamous cell carcinoma and melanoma via cell cycle control.

mir-145 Non-coding RNA in the species Homo sapiens

In molecular biology, mir-145 microRNA is a short RNA molecule that in humans is encoded by the MIR145 gene. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

mir-200

In molecular biology, the miR-200 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by binding and cleaving mRNAs or inhibiting translation. The miR-200 family contains miR-200a, miR-200b, miR-200c, miR-141, and miR-429. There is growing evidence to suggest that miR-200 microRNAs are involved in cancer metastasis.

mir-223 Mir-223

In molecular biology MicroRNA-223 (miR-223) is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. miR-223 is a hematopoietic specific microRNA with crucial functions in myeloid lineage development. It plays an essential role in promoting granulocytic differentiation while also being associated with the suppression of erythrocytic differentiation. miR-223 is commonly repressed in hepatocellular carcinoma and leukemia. Higher expression levels of miRNA-223 are associated with extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach and recurrent ovarian cancer. In some cancers the microRNA-223 down-regulation is correlated with higher tumor burden, disease aggressiveness, and poor prognostic factors. MicroRNA-223 is also associated with rheumatoid arthritis, sepsis, type 2 diabetes, and hepatic ischemia.

mir-31

miR-31 has been characterised as a tumour suppressor miRNA, with its levels varying in breast cancer cells according to the metastatic state of the tumour. From its typical abundance in healthy tissue is a moderate decrease in non-metastatic breast cancer cell lines, and levels are almost completely absent in mouse and human metastatic breast cancer cell lines. Mir-31-5p has also been observed upregulated in Zinc Deficient rats compared to normal in ESCC and in other types of cancers when using this animal model. There has also been observed a strong encapsulation of tumour cells expressing miR-31, as well as a reduced cell survival rate. miR-31's antimetastatic effects therefore make it a potential therapeutic target for breast cancer. However, these two papers were formally retracted by the authors in 2015.

In molecular biology mir-326 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-497 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology mir-885 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

MicroRNA-125 (miR-125) is a highly conserved microRNA family consisting of miR-125a and miR-125b. MiR-125 can be found throughout diverse species from nematode to humans. MiR-125 family members are involved in cell differentiation, proliferation and apoptosis as a result of targeting messenger RNAs related to these cellular processes. By affecting these cellular processes, miR-125 can cause promotion or suppression of pathological processes including carcinogenesis, muscle abnormalities, neurological disorders and pathologies of the immune system. Moreover, miR-125 also plays an important role in normal immune functions and was described to affect development and function of immune cells as well as playing role in immunological host defense in response to bacterial and viral infections.

References

  1. 1 2 Katoh M (2014). "Cardio-miRNAs and onco-miRNAs: circulating miRNA-based diagnostics for non-cancerous and cancerous diseases". Frontiers in Cell and Developmental Biology. 2: 61. doi: 10.3389/fcell.2014.00061 . PMC   4207049 . PMID   25364765.
  2. ↑ Yao X (2012). Regulation of A-type potassium channel Kv4.2 expression by FMRP and miR-324-5p (Ph.D. thesis). Emory University.
  3. 1 2 3 Gross C, Yao X, Engel T, Tiwari D, Xing L, Rowley S, et al. (September 2016). "MicroRNA-Mediated Downregulation of the Potassium Channel Kv4.2 Contributes to Seizure Onset". Cell Reports. 17 (1): 37–45. doi:10.1016/j.celrep.2016.08.074. PMC   5061042 . PMID   27681419.
  4. ↑ Stappert L, Borghese L, Roese-Koerner B, Weinhold S, Koch P, Terstegge S, et al. (2013). "MicroRNA-based promotion of human neuronal differentiation and subtype specification". PLOS ONE. 8 (3): e59011. Bibcode:2013PLoSO...859011S. doi: 10.1371/journal.pone.0059011 . PMC   3601127 . PMID   23527072.
  5. 1 2 3 Smalheiser NR, Lugli G, Rizavi HS, Torvik VI, Turecki G, Dwivedi Y (2012). "MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects". PLOS ONE. 7 (3): e33201. Bibcode:2012PLoSO...733201S. doi: 10.1371/journal.pone.0033201 . PMC   3302855 . PMID   22427989.
  6. 1 2 Wang K, Zhang DL, Long B, An T, Zhang J, Zhou LY, et al. (December 2015). "NFAT4-dependent miR-324-5p regulates mitochondrial morphology and cardiomyocyte cell death by targeting Mtfr1". Cell Death & Disease. 6 (12): e2007. doi:10.1038/cddis.2015.348. PMC   4720883 . PMID   26633713.
  7. ↑ Hervé M, Ibrahim EC (August 2016). "MicroRNA screening identifies a link between NOVA1 expression and a low level of IKAP in familial dysautonomia". Disease Models & Mechanisms. 9 (8): 899–909. doi:10.1242/dmm.025841. PMC   5007982 . PMID   27483351.
  8. ↑ Ellis KL, Cameron VA, Troughton RW, Frampton CM, Ellmers LJ, Richards AM (October 2013). "Circulating microRNAs as candidate markers to distinguish heart failure in breathless patients". European Journal of Heart Failure. 15 (10): 1138–47. doi: 10.1093/eurjhf/hft078 . PMID   23696613. S2CID   8373858.
  9. ↑ Kim J, Krichevsky A, Grad Y, Hayes GD, Kosik KS, Church GM, et al. (January 2004). "Identification of many microRNAs that copurify with polyribosomes in mammalian neurons". Proceedings of the National Academy of Sciences of the United States of America. 101 (1): 360–5. Bibcode:2004PNAS..101..360K. doi: 10.1073/pnas.2333854100 . PMC   314190 . PMID   14691248.
  10. ↑ Bompfünewerer AF, Flamm C, Fried C, Fritzsch G, Hofacker IL, Lehmann J, et al. (April 2005). "Evolutionary patterns of non-coding RNAs". Theory in Biosciences = Theorie in den Biowissenschaften. 123 (4): 301–69. CiteSeerX   10.1.1.144.5935 . doi:10.1016/j.thbio.2005.01.002. PMID   18202870. S2CID   7875269.
  11. ↑ Hariharan M, Scaria V, Pillai B, Brahmachari SK (December 2005). "Targets for human encoded microRNAs in HIV genes". Biochemical and Biophysical Research Communications. 337 (4): 1214–8. doi:10.1016/j.bbrc.2005.09.183. PMID   16236258.
  12. 1 2 Chen Y, Wang SX, Mu R, Luo X, Liu ZS, Liang B, et al. (June 2014). "Dysregulation of the miR-324-5p-CUEDC2 axis leads to macrophage dysfunction and is associated with colon cancer". Cell Reports. 7 (6): 1982–93. doi: 10.1016/j.celrep.2014.05.007 . PMID   24882011.
  13. ↑ "MIR324 microRNA 324 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-11-18.
  14. 1 2 "Homo sapiens (human) hsa-miR-324-5p | URS000005481D". RNAcentral. European Molecular Biology Laboratory.
  15. ↑ "MiRNA Entry for MI0000813". miRBase: the microRNA database. The University of Manchester.
  16. 1 2 "miRNA ID: hsa-miR-324-5p". TargetMiner: Prediction of miRNA Targets. Indian Statistical Institute.
  17. 1 2 Kuo WT, Yu SY, Li SC, Lam HC, Chang HT, Chen WS, et al. (October 2016). "MicroRNA-324 in Human Cancer: miR-324-5p and miR-324-3p Have Distinct Biological Functions in Human Cancer". Anticancer Research. 36 (10): 5189–5196. doi: 10.21873/anticanres.11089 . PMID   27798879.
  18. 1 2 Wang X. "predicted targets for hsa-miR-324-5p in miRDB". miRDB: predicted microRNA targets in animals. St. Louis: Department of Radiation Oncology, Washington University School of Medicine.
  19. ↑ "Predicted miRNA targets of miR-324-5p". TargetscanHuman 7.1. Whitehead Institute for Biomedical Research.
  20. 1 2 Xu HS, Zong HL, Shang M, Ming X, Zhao JP, Ma C, et al. (2014-03-30). "MiR-324-5p inhibits proliferation of glioma by target regulation of GLI1". European Review for Medical and Pharmacological Sciences. 18 (6): 828–32. PMID   24706306.
  21. ↑ Ferretti E, De Smaele E, Miele E, Laneve P, Po A, Pelloni M, et al. (October 2008). "Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells". The EMBO Journal. 27 (19): 2616–27. doi:10.1038/emboj.2008.172. PMC   2567402 . PMID   18756266.
  22. ↑ Song L, Liu D, Zhao Y, He J, Kang H, Dai Z, et al. (August 2015). "Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis". Biochemical and Biophysical Research Communications. 464 (3): 705–10. doi:10.1016/j.bbrc.2015.07.004. PMID   26166821.
  23. ↑ Liu SM, Lu J, Lee HC, Chung FH, Ma N (October 2014). "miR-524-5p suppresses the growth of oncogenic BRAF melanoma by targeting BRAF and ERK2". Oncotarget. 5 (19): 9444–59. doi:10.18632/oncotarget.2452. PMC   4253445 . PMID   25275294.
  24. ↑ Cao L, Xie B, Yang X, Liang H, Jiang X, Zhang D, et al. (2015). "MiR-324-5p Suppresses Hepatocellular Carcinoma Cell Invasion by Counteracting ECM Degradation through Post-Transcriptionally Downregulating ETS1 and SP1". PLOS ONE. 10 (7): e0133074. Bibcode:2015PLoSO..1033074C. doi: 10.1371/journal.pone.0133074 . PMC   4503725 . PMID   26177288.
  25. ↑ Liu C, Li G, Yang N, Su Z, Zhang S, Deng T, Ren S, Lu S, Tian Y, Liu Y, Qiu Y (2017). "miR-324-3p suppresses migration and invasion by targeting WNT2B in nasopharyngeal carcinoma". Cancer Cell International. 17: 2. doi: 10.1186/s12935-016-0372-8 . PMC   5209830 . PMID   28053597.
  26. 1 2 Tang B, Xu A, Xu J, Huang H, Chen L, Su Y, et al. (January 2018). "MicroRNA-324-5p regulates stemness, pathogenesis and sensitivity to bortezomib in multiple myeloma cells by targeting hedgehog signaling". International Journal of Cancer. 142 (1): 109–120. doi: 10.1002/ijc.31041 . PMID   28905994.
  27. ↑ Sun GL, Li Z, Wang WZ, Chen Z, Zhang L, Li Q, et al. (June 2018). "miR-324-3p promotes gastric cancer development by activating Smad4-mediated Wnt/beta-catenin signaling pathway". Journal of Gastroenterology. 53 (6): 725–739. doi:10.1007/s00535-017-1408-0. PMC   5971041 . PMID   29103082.
  28. ↑ Lin H, Zhou AJ, Zhang JY, Liu SF, Gu JX (November 2018). "MiR-324-5p reduces viability and induces apoptosis in gastric cancer cells through modulating TSPAN8". The Journal of Pharmacy and Pharmacology. 70 (11): 1513–1520. doi:10.1111/jphp.12995. PMID   30159900. S2CID   52122292.
  29. ↑ Fransén E, Tigerholm J (July 2010). "Role of A-type potassium currents in excitability, network synchronicity, and epilepsy". Hippocampus. 20 (7): 877–87. doi:10.1002/hipo.20694. PMC   3222850 . PMID   19777555.
  30. ↑ Brennan GP, Henshall DC (February 2018). "microRNAs in the pathophysiology of epilepsy". Neuroscience Letters. 667: 47–52. doi:10.1016/j.neulet.2017.01.017. PMID   28104433. S2CID   3447211.
  31. ↑ Li Y, Kowdley KV (October 2012). "MicroRNAs in common human diseases". Genomics, Proteomics & Bioinformatics. 10 (5): 246–53. doi:10.1016/j.gpb.2012.07.005. PMC   3611977 . PMID   23200134.
  32. ↑ Schouten M, Fratantoni SA, Hubens CJ, Piersma SR, Pham TV, Bielefeld P, Voskuyl RA, Lucassen PJ, Jimenez CR, Fitzsimons CP (July 2015). "MicroRNA-124 and -137 cooperativity controls caspase-3 activity through BCL2L13 in hippocampal neural stem cells". Scientific Reports. 5: 12448. Bibcode:2015NatSR...512448S. doi:10.1038/srep12448. PMC   4513647 . PMID   26207921.
  33. ↑ Bot AM, Dębski KJ, Lukasiuk K (2013). "Alterations in miRNA levels in the dentate gyrus in epileptic rats". PLOS ONE. 8 (10): e76051. Bibcode:2013PLoSO...876051B. doi: 10.1371/journal.pone.0076051 . PMC   3795667 . PMID   24146813.
  34. ↑ Tiwari D, Peariso K, Gross C (January 2018). "MicroRNA-induced silencing in epilepsy: Opportunities and challenges for clinical application". Developmental Dynamics. 247 (1): 94–110. doi:10.1002/dvdy.24582. PMC   5740004 . PMID   28850760.
  35. ↑ Meydan C, Shenhar-Tsarfaty S, Soreq H (September 2016). "MicroRNA Regulators of Anxiety and Metabolic Disorders". Trends in Molecular Medicine. 22 (9): 798–812. doi:10.1016/j.molmed.2016.07.001. PMID   27496210.
  36. 1 2 Balakathiresan NS, Chandran R, Bhomia M, Jia M, Li H, Maheshwari RK (October 2014). "Serum and amygdala microRNA signatures of posttraumatic stress: fear correlation and biomarker potential". Journal of Psychiatric Research. 57: 65–73. doi:10.1016/j.jpsychires.2014.05.020. PMID   24998397.
  37. ↑ Narahari A, Hussain M, Sreeram V (2017). "MicroRNAs as Biomarkers for Psychiatric Conditions: A Review of Current Research". Innovations in Clinical Neuroscience. 14 (1–2): 53–55. PMC   5373795 . PMID   28386521.
  38. ↑ Hashimoto Y, Akiyama Y, Yuasa Y (2013-05-08). "Multiple-to-multiple relationships between microRNAs and target genes in gastric cancer". PLOS ONE. 8 (5): e62589. Bibcode:2013PLoSO...862589H. doi: 10.1371/journal.pone.0062589 . PMC   3648557 . PMID   23667495.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.