mature mirnas are short single - stranded rna molecules , approximately 1923 nucleotides in length .
the mirna sequence is encoded in a stem - loop structure in the primary transcript that is cleaved in the nucleus by the ribonuclease iii enzyme drosha to form the precursor mirna ( pre - mirna ) .
the pre - mirna is subsequently exported to the cytoplasm by the exportin and then is cleaved by another ribonuclease iii enzyme dicer to form mature mirna [ 13 ] .
mature mirnas can regulate the expression of a large number of genes at the posttranscriptional level .
mirna is partially complementary to the sequence of mirna recognition elements ( mre ) in the 3 untranslated regions ( utrs ) of target mrnas .
the seed sequence with seven nucleotides in mirna determines the specificity of mrna targeting , whereas the remaining mirna sequence is supposed to stabilize the mirna - target complex .
mirna can inhibit translation of target mrnas by blocking protein translation machinery or by sequestering the mrna transcript away from ribosomal interaction .
mirna can also induce target mrna degradation in a similar way like rna interference [ 1 , 5 ] .
mirnas have been identified in a wide range of species , and computational analysis shows that nearly 30% of protein - coding genes can be modulated by mirnas . in general , mirnas negatively regulate the expression of their targets . however , it is also reported that mir-369 - 3p can upregulate the expression of its target , tumor necrosis factor- ( tnf- ) .
mirnas have been demonstrated to play important roles in many biological processes , such as cell cycle control , proliferation , apoptosis , differentiation , metabolism , hemopoiesis , and development .
a rapidly growing body of evidence shows that mirnas also have comprehensive functions in tumor progression .
some mirnas may function as oncogenes ( also called oncomirs ) while some mirnas are supposed to be tumor suppressors .
the importance of mirnas in cancer is highlighted by the fact that half of all mirna genes are located in cancer - associated regions or fragile sites , which are frequently altered or deleted in cancer .
many tumor types show unique mirna signatures ; thus , mirnas may be of use in cancer diagnosis and prognosis [ 11 , 12 ] .
pituitary adenomas are usually benign intracranial neoplasms , accounting for 1015% of diagnosed brain tumors .
pituitary adenomas can be derived from a single mutant cell of five differentiated cell types within pituitary gland : somatotropes , lactotropes , corticotropes , thyrotropes , and gonadotropes , which , respectively , secrete growth hormone ( gh ) , prolactin ( prl ) , adrenocorticotrophic hormone ( acth ) , thyroid - stimulating hormone ( tsh ) , and gonadotropins ( follicle - stimulating hormone ( fsh ) and luteinizing hormone ( lh ) ) . according to the hormonal activity
, pituitary adenomas can be defined as  functioning ,  causing endocrine dysfunction such as cushing 's disease in acth - secreting pituitary adenomas , acromegaly in gh - secreting pituitary adenomas , galactorrhea and amenorrhea in prl - secreting pituitary adenomas , and hyperthyroidism in tsh - secreting pituitary adenomas . on the other hand , nonfunctioning pituitary adenomas ( nfa ) do not give rise to hormone hypersecretion .
pituitary adenomas might be small lesions with slow growth . however , some pituitary adenomas grow rapidly and cause tumor mass effect , the local compressive effect of large pituitary tumors on brain structures and cranial nerves
. they can also invade downwards into the paranasal sinuses , laterally into the cavernous sinuses and upwards into the parenchyma of the brain .
occasionally , malignant pituitary carcinomas metastasize to distant locations in the central nervous system , lymph nodes , liver , and other sites throughout the body . in recent years
nevertheless , the correlation and function of mirnas and their target genes in pathogenesis of pituitary adenomas remain largely unknown .
only a small number of mirnas with their target genes in pituitary adenomas have been validated so far . in this review
, we summarize recent advances in the study of mirnas and their validated or potential targets in pituitary adenomas and discuss the future perspectives .
aberrant expressions of mirnas have been demonstrated so far ( table 1 ) . mir-15a and mir-16 - 1 are the first two mirnas shown to have differential expression in pituitary adenomas . mir-15a and mir-16 - 1 genes are located at chromosome 13q14 , a region which is frequently deleted in pituitary tumors .
previous studies have suggested that the genes in this locus may be responsible for the progression of pituitary adenoma to a more aggressive form . in 2005 ,
mir-15a and mir-16 - 1 were reported to have lower expression in both gh - secreting and prl - secreting pituitary adenomas than in normal tissues , and their downregulation was correlated with greater tumor volume and impaired secretion of p43 , a potent anticancer cytokine , suggesting that mir-15a and mir-16 - 1 may function as tumor suppressors and their inactivation may contribute to tumor growth in pituitary adenomas . in another study on acth - secreting pituitary tumors , mir-15a and mir-16
were also expressed at a lower level , but no association between mirnas expression and tumor size was observed in this study .
this is in accordance with the result of a subsequent report which showed no correlation between downregulation of mir-15a and gh - secreting pituitary tumor size .
mutations in mir-16 - 1 gene have been reported to be partially responsible for its altered expression in chronic lymphocytic leukemia ( cll ) patients .
thus , it is worth exploring whether there are similar mutations in pituitary adenoma patients .
family members are located at chromosomal regions that are often altered or deleted in human tumors .
downregulation of let-7 has been reported in breast , lung , colon , and others cancers [ 3033 ] and let-7 is considered a tumor suppressor by targeting ras oncogene .
recently , some studies revealed that high - mobility group a2 ( hmga2 ) is negatively regulated by the let-7 mirnas in vitro [ 35 , 36 ] .
hmga2 plays diverse roles in many biological processes such as embryogenesis , differentiation , and neoplastic transformation .
overexpression of hmga2 is a hallmark of various tumors , including pituitary adenomas , and is associated with highly malignancy [ 38 , 39 ] .
the transgenic mice with overexpressed hmga2 developed pituitary adenomas , indicating that hmga2 may be involved in pituitary tumorigenesis . in 2009 ,
hmga2 was frequently upregulated in pituitary adenomas including prl , acth , fsh / lh , or null cell adenomas but relatively rare in gh and mixed gh / prl adenomas .
hmga2 overexpression and the decrease of let-7 were significantly correlated with tumor proliferation , growth , invasion , and tumor grade , which lead to a hypothesis that let-7 may also function as a tumor suppressor in pituitary adenomas by targeting hmga2 .
decreased expression of let-7a in pituitary adenomas was also reported in other studies [ 27 , 41 ] , suggesting the general downregulation of let-7 in pituitary adenomas . on the other hand , some other mirnas such as mir-98 can also regulate hmga2 expression , indicating that hmga2 may have multiple mirnas regulators . during pituitary development , let-7b / c
was proposed to operate with the rna - binding protein ksrp in a negative feedback loop , in which ksrp induces the maturation of let-7b / c , and let-7b / c posttranscriptionally downregulates the expression of ksrp itself . as pituitary adenomas can be derived from differentiated cell types within pituitary gland , different subtypes of pituitary adenomas could display distinct mirna profiles , and these specific profiles might be useful to distinguish pituitary adenoma subtypes . in 2007 ,
the most representative ones were mir-212 , mir-026a , mir-150 , mir-152 , mir-191 , and mir-192 , which were upregulated in pituitary adenomas , while mir-024 - 1 and mir-098 were downregulated in tumor samples .
twenty - nine mirnas were identified to be able to predict pituitary adenoma histotype ( acth- , gh- , prl - secreting adenomas , and nfa ) . for the limit of sample numbers ,
the authors only analyzed the association of deregulated mirnas and tumor diameter in the nfa group .
five mirnas were upregulated ( mir-140 , mir-099a , mir-099b , mir-030b , and mir-030c ) and only one ( mir-138 - 2 ) was downregulated in macroadenomas compared to microadenomas . in 2009 , amaral et al . investigated the differential expression of some mirnas in acth - secreting pituitary tumors .
in addition to the decrease of let-7a , mir-15a , and mir-16 , they also found underexpression of mir-21 , mir-141 , mir-143 , mir-145 , and mir-150 in acth - secreting pituitary adenomas compared with normal pituitary tissues . among these mirnas ,
mir-143 expression was decreased in human lung and colorectal cancers [ 46 , 47 ] and was reported to inhibit kras translation in colorectal cancer cell .
mir-145 was downregulated in human breast , lung , and colorectal cancers [ 30 , 46 , 47 , 49 ] .
mir-145 could regulate the expression of various targets in different tumors : fscn1 in esophageal squamous cell carcinoma , oct4 , egfr , and nudt1 in lung adenocarcinoma [ 51 , 52 ] , and fli1 in colon cancer .
mir-150 was overexpressed in hematopoietic progenitor / stem cells   and was demonstrated to target notch3 in human t - cell development in a recent study .
studies were conducted with the aim of investigating the aberrant expression of mirnas in gh - secreting pituitary adenomas . in 2010 , mao et al .
identified totally fifty - two mirnas to be differentially expressed in gh - secreting pituitary adenomas .
mir-184 , mir-524 - 5p , mir-629 , and mir-766 were upregulated , while mir-124 , mir-222 , mir-32 , mir-744 , and mir-765 were downregulated . in 2012 , another set of mirnas were identified to be differentially expressed in gh - secreting pituitary adenomas .
eighteen mirnas , including mir-34b , mir-326 , mir-432 , mir-548c-3p , mir-570 , and mir-603 , were drastically and constantly downregulated in gh adenomas , whereas only mir-320 was significantly upregulated . mir-34b and
mir-548c-3p were demonstrated to regulate both hmga1 and hmga2 expression , whereas mir-326 , mir-432 , and mir-570 target hmga2 only . mir-326 and mir-603 could decrease the expression of the e2 transcription factor 1 , e2f1 .
besides , mir-107 was found to be overexpressed in gh - secreting and nonfunctioning pituitary adenomas and inhibited the expression of pituitary tumor suppressor gene aryl hydrocarbon receptor - interacting protein ( aip ) . recently , palumbo et al
. identified 17 mirnas which were differentially expressed in gh - secreting pituitary tumors . specifically , five mirnas ( mir-26b , mir-26a , mir-212 , mir-107 , and mir-103 ) were upregulated and twelve mirnas ( mir-125b , mir-141 , mir-144 , mir-164 , mir-145 , mir-143 , mir-15b , mir-16 , mir-186 , let-7b , let-7a3 , and mir-128 ) were downregulated .
mir-26b and mir-128 controlled pituitary cell properties through regulation of their direct targets , pten , and bmi1 , respectively .
mirnas are also dysregulated in nonfunctioning pituitary adenomas ( nfa ) . in 2011 , butz et al .
expressions of smad3 , smad6 , smad9 , meg , and dlk1 were significantly decreased in nfa . through pathway analysis and in silico target prediction
, a specific subset of mirnas was identified that may potentially downregulate tgf- signaling pathway in nfa .
five mirnas predicted to target smad3 ( mir-135a , mir-140 - 5p , mir-582 - 3p , mir-582 - 5p , and mir-938 ) were overexpressed , of which mir-140 - 5p has already been validated to target smad3 directly .
in addition , an inverse correlation between tumor size and the expression of eighteen mirnas was observed .
six mirnas of them ( mir-450b-5p , mir-424 , mir-503 , mir-542 - 3p , mir-629 , and mir-214 ) were significantly underexpressed , while one mirna ( mir-592 ) was significantly overexpressed in nfa compared to normal pituitary tissues . in another study , mir-124a was the most upregulated mirna , and mir-31 was the most downregulated mirna in nonfunctioning pituitary adenomas . in gonadotropin - secreting pituitary adenomas , a study demonstrated that mir-10b was upregulated and mir-503 was downregulated .
furthermore , the integration and coordination of hormones and pituitary cells are important for the regulatory function of pituitary tissues .
gonadotropin - releasing hormone ( gnrh ) acts on pituitary gonadotropes to stimulate lh and fsh synthesis and secretion .
gnrh induces expressions of mir-132 and mir-212 in lt2 pituitary gonadotrope cells to regulate cellular morphology and migration .
the p250rhogap protein is a downstream target of mir132/212 and its downregulation is involved in the morphological change and migration altered by gnrh .
it is well known that the dysfunction of cell cycle control is a critical step in initiation and progression of human cancers .
some oncoproteins or tumor suppressors play important roles in cell cycle control by interacting with critical cell cycle regulators , such as cyclin , cyclin - dependent - kinase ( cdk ) , or cell cycle inhibitors . during tumor progression
, the genes involved in cell cycle control often have aberrant expression , resulting in unlimited tumor cell growth .
some reports suggested that the deregulated mirnas might also regulate cell cycle of pituitary adenomas at the post - transcriptional level ( figure 1 ) .
mir-128a , mir-155 , and mir-516a-3p target 3-utr of wee1 , and exogenous overexpression of these mirnas inhibited wee1 expression .
mir-128a is a brain - enriched mirna and was reported to be decreased in pituitary adenomas .
its ectopic overexpression reduced neuroblastoma cell motility and invasiveness , suggesting its tumor suppressive role .
mir-516a-3p was involved in glioblastoma development   and was associated with progression of breast cancer .
these mirnas may take part in the regulation of cell cycle in pituitary adenomas together with other related mirnas .
hmga2 is associated with the e1a - regulated transcriptional repressor p120 ( e4f ) , interfering with p120 ( e4f ) binding to the cyclin a promoter .
ectopic expression of hmga2 resulted in the activation of cyclin a promoter and induction of endogenous cyclin a expression .
moreover , chromatin immunoprecipitation experiments showed that hmga2 was associated with cyclin a promoter only when the gene was transcriptionally activated .
these data indicate cyclin a as a cellular target of hmga2 and , for the first time , lead to a mechanism of hmga2-dependent cell cycle regulation .
thus , let-7 , as a regulator of hmga2 , may exert its effects in cell cycle control of pituitary adenomas by targeting hmga2 . mir-23b and mir-130b , which were reduced in gh , gonadotroph , and nfpa adenomas ,
overexpression of mir-23b and mir-130b arrested the cells in the g1 and g2 phase of the cell cycle . recently , a study revealed that mir-15a and mir-16 - 1 cluster could modulate prostate cancer by targeting multiple genes , including cyclin d1 . regarding the deregulation in pituitary adenomas , mir-15a and mir-16 - 1 may exert their roles as tumor suppressors by regulating cell cycle .
previous study has shown that mir-126 could modulate phosphatidylinositol 3-kinase ( pi3k ) signaling by limiting the pi3k regulatory subunit beta ( p85b ) .
loss of mir-126 would eliminate the check point and increase pi3k signaling , which facilitate tumor growth during colon carcinogenesis .
mir-145 was downregulated in gh - secreting pituitary adenomas , which is in line with the results in 11 samples of cortitropinomas .
the potential targets of mir-145 include myc , kras , fos , yes , fli , cyclin d2 , and mapk transduction proteins , indicating that mir-145 might function in cell cycle control by targeting multiple genes .
mir-503 has been validated to directly target cyclin d1 and is thought to be a tumor suppressor .
furthermore , an important potential target of mir-503 is the cell cycle regulator cdc25 . mir-26b and mir-128
were found to directly regulate pten and bmi1 , respectively . moreover , mir-128 regulated pten expression and akt activity in the pituitary tumor cells by interfering with the binding of bmi1 to pten promoter .
since pten - akt pathway plays important roles in cell cycle control , mir-26b and mir-128 might regulate cell cycle through pten - akt pathway .
moreover , mir-26a was also overexpressed in acth - secreting pituitary adenomas and plays an important role in cell cycle control by modulating protein kinase c delta .
apoptosis , the process of programmed cell death , is an important barrier for tumor cells . during malignant transformation and tumor progression
, tumor cells have to escape this regulated cell death to obtain an advantage in growth and expansion . at the early stage of apoptosis
, cells receive death signals , and then the  apoptotic trigger  is controlled by pro- or antiapoptotic members of b - cell lymphoma 2 ( bcl-2 ) family and other regulatory proteins .
accumulating evidence have shown that mirnas can regulate cancer cell apoptosis by targeting bcl-2 family or other apoptosis regulators ( figure 1 ) . mir-15a and mir-16 - 1 were demonstrated to induce apoptosis by targeting bcl-2 in cll .
bcl-2 is a founding member of the bcl-2 family , a family of antiapoptotic proteins governing mitochondrial death signaling .
bcl-2 is frequently overexpressed in many types of human cancers , including carcinomas , lymphomas , and leukemias . in cll
, some other apoptosis related genes were identified to be targets of mir-15a and mir-16 - 1 cluster , such as mcl1 , which could enhance cell survival by inhibiting apoptosis .
therefore , it is possible that , in pituitary adenomas , mir-15a and mir-16 - 1 influence apoptosis by targeting multiple antiapoptotic genes . besides , mir-214 and mir-629 ,
two mirnas overexpressed in nfa and negatively correlated with tumor size , also potentially target bcl2 .
mir-21 was differentially expressed in acth - secreting pituitary adenomas compared with normal pituitary tissues .
mir-21 has been identified to be upregulated in human breast , lung , colorectal and other cancers [ 30 , 46 , 49 , 75 ] .
suppression of mir-21 by antisense oligonucleotides or mir-21 knockdown was associated with increased apoptotic activity and inhibition of tumor cell growth , probably by downregulating the target tumor suppressor genes .
mir-21 may exert its function in apoptosis by targeting tumor suppressor pdcd4   and pten .
overexpression of pdcd4 was able to result in apoptotic death , and pten can induce apoptosis through phosphoinositol-3-kinase / akt dependent and independent pathways .
putative targets of mir-212 include death effector domain - containing protein ( dedd ) , a protein involved in apoptotic signaling , as well as other proteins participating in apoptosis .
mir184 was markedly upregulated in gh - secreting pituitary adenomas and was correlated with tumor diameter .
contrary to that , another study reported that ectopic overexpression of mir-184 resulted in increased apoptosis .
study of cheng et al . suggested that the upregulated mir-150 , mir-152 , mir-191 , and mir-192 may also be involved in apoptosis .
mir-26b was found to be upregulated in gh - secreting pituitary tumors and directly regulate pten .
mir-200c , which has been characterized as a tumor suppressor or oncogene in different cancers , also inhibited apoptosis in pituitary adenoma cells by targeting the pten / akt signaling pathway .
intriguingly , a novel marine drug , sz-685c that was isolated from the secondary metabolites of a mangrove endophytic fungus was reported to induce apoptosis of mmq pituitary tumor cells by downregulating mir-200c .
tgf- has been shown to inhibit proliferation and induce apoptosis in hp75 cells , a cell line derived from a clinically nfa .
thereby , the mirnas targeting tgf- signaling ( mir-135a , mir-140 - 5p , mir-582 - 3p , mir-582 - 5p , and mir-938 ) may have effects in apoptosis .
however , as tgf- can also promote cancer cell invasion by inducing epithelial - mesenchymal transition ( emt ) , it is rational to conclude that mirnas targeting tgf- pathway may suppress invasion and metastasis by blocking emt , as mir-300 does in human epithelial cancer .
therefore , mirnas that regulate tgf- pathway play controversial roles in tumor initiation and progression .
deregulation of bmi1 has been revealed to affect apoptosis ; thus , mir-128 , which was downregulated in gh - secreting pituitary tumors , could also affect apoptosis by directly regulating bmi1 .
these data together lead to the hypothesis that many mirnas may function in a network to regulate apoptosis in pituitary adenomas .
although invasion and metastasis are rare in pituitary tumors , studies provide some clues of mirnas ' function in pituitary tumor invasion and metastasis ( figure 1 ) .
significant correlation between hmga2 overexpression and tumor cell invasion has been detected in breast cancer and gastric cancer [ 89 , 90 ] . in oral squamous cell carcinomas ,
strong staining of hmga2 and loss of e - cadherin expression were observed at the invasive front of tumor .
previous studies also demonstrated that tumor - specific downregulation of e - cadherin and h - cadherin was related to invasiveness of pituitary adenoma .
hmga2 may be involved in tumor cell invasion due to its association with epithelial - mesenchymal transition that facilitates tumor cell invasion .
since let-7 regulates hmga2 expression in pituitary adenomas , let-7 may also take a role in pituitary adenoma invasion .
in amaral et al . 's study , although no association between mirnas expression and tumor size was observed , the patients with acth - secreting pituitary tumors expressing reduced mir-141 had more chance of remission after transsphenoidal surgery , suggesting that mir-141 may regulate pituitary genes involved in tumor growth and local invasion .
pttg protein 1 is a target of both mir-126 and mir-381 , which were downregulated in gh - secreting pituitary adenomas .
aggressive pituitary adenomas and carcinomas frequently have a deletion in regions near the rb gene [ 94 , 95 ] . in 2010 , stilling et al .
more mirnas were deregulated between pituitary adenomas and normal pituitaries compared to carcinomas and normal pituitaries . in pituitary carcinomas compared to acth adenomas , mir-122 and mir-493 were upregulated , and , in all three metastatic sites of acth carcinomas , mir-122 expression was markedly increased . recently ,
palumbo et al . identified mir-26b to be upregulated and mir-128 to be downregulated in gh - secreting pituitary tumors .
inhibition of mir-26b and overexpression of mir-128 suppressed colony formation and invasiveness of pituitary tumor cells .
interestingly , the inhibition of mir-26b and overexpression of mir-128 had a synergistic effect on suppressing the tumorigenicity and invasiveness of pituitary tumors . since deregulation of pten and bmi1 correlates with the invasive and metastatic phenotype of several human cancer types [ 97 , 98 ] , it is possible that mir-26b and mir-128 regulate invasiveness of pituitary tumor cells by directly targeting pten and bmi1 , respectively .
although metastatic pituitary carcinomas are rare , these data suggest that altered expression of mirnas may provide diagnostic information to distinguish pituitary adenomas and carcinomas before they metastasize .
the symptoms of mass effect and hormonal hypersecretion caused by pituitary adenomas could be reversed by surgical resection or debulking of the adenoma , radiotherapy , or medical treatment .
medical treatment is the primary choice for prolactinomas and the secondary option for acromegaly , cushing 's disease , gonadotropin - secreting tumours , and tsh - secreting adenomas .
some studies provide evidence that mirnas were differentially expressed before and after pharmacological treatment , and the altered mirna profile could provide useful information of responsiveness of pituitary adenomas patients to pharmacological treatment ( figure 1 ) . in 2007 ,
a microarray was carried out to analyze the mirna profiles in pituitary adenomas and normal pituitary samples . to elucidate whether mirnas profile is altered by pharmacological treatment ,
differentially expressed mirnas were identified in nfa from patients with pharmacological treatment or patients without treatment .
six mirnas were found to be differentially expressed : mir-29b , mir-29c , and mir-200a were upregulated , while mir-134 , mir-148 , and mir-155 were downregulated after treatment .
thus , the mirna expression could differentiate treated patient samples from nontreated patient samples . in 2010 ,
another study aimed to identify altered expression of mirnas in gh - secreting pituitary adenomas .
fifteen pituitary adenomas patients were treated with lanreotide for four months before surgery , while six patients did not receive any presurgical medical treatments .
patients with > 50% reduction of gh secretion after lanreotide treatment were considered somatostatin analogs ( ssa ) responders , while patients with < 50% gh secretion were considered ssa nonresponders .
thirteen mirnas were differentially expressed between gh - secreting pituitary adenomas from patients with lanreotide treatment and those without treatment .
eight mirnas ( mir-183 , mir-193a-5p , mir-222 , mir-516b , mir-524 - 5p , mir-601 , and mir-629 , 99b ) were upregulated and five mirnas ( mir-124 , mir-32 , mir-574 - 5p , mir-744 , and mir-96 ) were downregulated .
putative targets of these mirnas are mainly igfbp family members , igfals , scp1 , and matrix metalloproteinase-9 .
accumulating evidence demonstrates that a large number of mirnas have altered expression in pituitary adenomas , and these mirnas may play important roles in tumor progression by targeting multiple genes .
the molecular mechanism of the regulation of mirnas in pituitary adenomas is still a mystery .
some proofs indicate that genetic or epigenetic alterations may contribute to the deregulated expression of mirnas .
for example , mutations in the mir-16 - 1 gene have been reported to be partially responsible for its aberrant expression in cll patients , and expressions of mir-124 and mir-203 are decreased because of cpg methylation .
some mirnas have been demonstrated to target multiple genes , indicating that they may have different roles in pituitary tumors . on the other hand ,
a gene involved in pituitary adenomas progression can be modulated by more than one mirna .
therefore , the mirnas and their targets could regulate pituitary adenomas progression in a complex network .
advances in the technology to investigate mirnas make it easier and faster to explore more exactly the roles of mirnas in pituitary adenomas . as some mirnas signatures can be used to distinguish pituitary adenomas and normal pituitaries and even subtypes of pituitary tumors , it is also possible to develop mirna based diagnosis and therapies of pituitary adenomas .
the knowledge of pituitary pathogenesis is still limited . continuing study on mirnas and their targets will shed more light on mechanisms of pituitary adenomas .
 micrornas ( mirnas ) are a class of recently identified noncoding rnas that regulate gene expression at posttranscriptional level . due to the large number of genes regulated by mirnas , 
 mirnas play important roles in many cellular processes . 
 emerging evidence indicates that mirnas are dysregulated in pituitary adenomas , a class of intracranial neoplasms which account for 1015% of diagnosed brain tumors . 
 deregulated mirnas and their targets contribute to pituitary adenomas progression and are associated with cell cycle control , apoptosis , invasion , and pharmacological treatment of pituitary adenomas . 
 to provide an overview of mirnas dysregulation and functions of these mirnas in pituitary adenoma progression , we summarize the deregulated mirnas and their targets to shed more light on their potential as therapeutic targets and novel biomarkers . 
1. MicroRNAs
2. Pituitary Adenomas
3. MicroRNAs in Pituitary Adenomas
4. Conclusion and Future Perspectives