SATB1 Expression Research Articles

Pathologic evaluation of the solid variant of aneurysmal bone cysts with USP6 rearrangement with an emphasis on the frequent diagnostic pitfalls.

The solid variant of aneurysmal bone cyst (SVABC) is very uncommon and frequently misdiagnosed. We reevaluated and summarized the clinicopathologic features of 17 SVABCs and further discussed the use of this nomenclature to differ SVABCs from extragnathic giant cell reparative granuloma (GCRG) in the setting of the USP6 rearrangement era. The immunohistochemical markers included α-SMA, SATB2, AE1/AE3, Ki67, S100, CD68 and P63. USP-6 status was detected by fluorescence in situ hybridization using a break-apart probe. The 17 patients with SVABCs comprised 10 males and 7 females ranging in age from 4 to 70 years. The involved locations included the long bone (n = 11), hand (n = 4), rib (n = 1) and vertebra (n = 1). The lesions were characterized by proliferated spindle cells with scattered giant cells and hemorrhages with variable positive α-SMA, SATB2, CD68 and Ki-67 expression. All patients had USP6 rearrangements without H3F3A glycine 34 mutations. Our study reveals that SVABC shares similar clinical and histologic features with other bone lesions, which may lead to an erroneous diagnosis. The presence of an USP-6 rearrangement contributes to the diagnosis SVABC; SVABC and most of the previously documented extragnathic GCRGs may be considered within the umbrella of primary aneurysmal bone cysts.

Maternal Obesity Modulates Expression of Satb2 in Hypothalamic VMN of Female Offspring.

Maternal obesity during pregnancy is associated with a greater risk of poor health outcomes in offspring, including obesity, metabolic disorders, and anxiety, however the incidence of these diseases differs for males and females. Similarly, animal models of maternal obesity have reported sex differences in offspring, for both metabolic outcomes and anxiety-like behaviors. The ventromedial nucleus of the hypothalamus (VMN) is a brain region known to be involved in the regulation of both metabolism and anxiety, and is well documented to be sexually dimorphic. As the VMN is largely composed of glutamatergic neurons, which are important for its functions in modulating metabolism and anxiety, we hypothesized that maternal obesity may alter the number of glutamatergic neurons in the offspring VMN. We used a mouse model of a maternal high-fat diet (mHFD), to examine mRNA expression of the glutamatergic neuronal marker Satb2 in the mediobasal hypothalamus of control and mHFD offspring at GD17.5. We found sex differences in Satb2 expression, with mHFD-induced upregulation of Satb2 mRNA in the mediobasal hypothalamus of female offspring, compared to controls, but not males. Using immunohistochemistry, we found an increase in the number of SATB2-positive cells in female mHFD offspring VMN, compared to controls, which was localized to the rostral region of the nucleus. These data provide evidence that maternal nutrition during gestation alters the developing VMN, possibly increasing its glutamatergic drive of offspring in a sex-specific manner, which may contribute to sexual dimorphism in offspring health outcomes later in life.

Differential timing of a conserved transcriptional network underlies divergent cortical projection routes across mammalian brain evolution

A unique combination of transcription factor expression and projection neuron identity demarcates each layer of the cerebral cortex. During mouse and human cortical development, the transcription factor CTIP2 specifies neurons that project subcerebrally, while SATB2 specifies neuronal projections via the corpus callosum, a large axon tract connecting the two neocortical hemispheres that emerged exclusively in eutherian mammals. Marsupials comprise the sister taxon of eutherians but do not have a corpus callosum; their intercortical commissural neurons instead project via the anterior commissure, similar to egg-laying monotreme mammals. It remains unknown whether divergent transcriptional networks underlie these cortical wiring differences. Here, we combine birth-dating analysis, retrograde tracing, gene overexpression and knockdown, and axonal quantification to compare the functions of CTIP2 and SATB2 in neocortical development, between the eutherian mouse and the marsupial fat-tailed dunnart. We demonstrate a striking degree of structural and functional homology, whereby CTIP2 or SATB2 of either species is sufficient to promote a subcerebral or commissural fate, respectively. Remarkably, we reveal a substantial delay in the onset of developmental SATB2 expression in mice as compared to the equivalent stage in dunnarts, with premature SATB2 overexpression in mice to match that of dunnarts resulting in a marsupial-like projection fate via the anterior commissure. Our results suggest that small alterations in the timing of regulatory gene expression may underlie interspecies differences in neuronal projection fate specification.

SATB2 is frequently expressed in ossifying and non-ossifying peripheral oral fibroma of the gingival region but not in reactive fibromatous lesions from other intraoral sites

Ossifying and non-ossifying peripheral oral fibromas (POF) of the gingival and alveolar mucosa are localized, cellular, small fibrous nodular lesions likely resulting from diverse external/ internal physical and chemical irritation or injuries. A central nidus of metaplastic woven bone characterizes and defines the ossifying variant. The inherent tendency of these lesions to ossify remains elusive. We herein analyze SATB2 expression as osteoblastic transcription and differentiation factor in 28 gingival POFs (10 of them ossifying) and compare them to 28 fibrous lesions from different non-gingival intraoral sites. Strong to moderate diffuse nuclear SATB2 immunoreactivity was detected in all ossifying (10/10; 100%) and in 8/18 (44%) non-ossifying gingival POFs, but in only 1/28 (3%) non-gingival oral reactive nodular fibrous lesions. This study illustrates for the first-time consistent expression of the osteoblastic marker SATB2 in ossifying and most of non-ossifying POFs of the gingival area but lack of this marker in reactive fibrous lesions from other oral cavity sites. This finding is in line with the proposed origin of gingival POFs from periodontal ligaments and may explain the frequent ossification observed in them. It is mandatory to consider this finding when assessing biopsies from SATB2-positive oral cavity neoplasms to avoid misinterpretation.

MiR-1301 promotes adipogenic and osteogenic differentiation of BMSCs by targeting Satb2.

Bone marrow mesenchymal stem cells (BMSCs) have the ability to differentiate into several cell lines and are critical for skeletal microenvironment and bone development. MiR-1301 is involved in multiple pathological and physiological processes. However, miR-1301's role in BMSCs adipogenic and osteogenic differentiation remains unclear. Rat BMSCs were isolated and randomly divided into control group, miR-1301 group, and miR-1301 siRNA group followed by analysis of the expression of miR-1301, Bax, Bcl-2, UNX2, and OPN, as well as FABP4 and PPARγ2 by Real Time-PCR. Cell proliferation was assessed by MTT assay and the relationship between miR-1301 and Satb2 was evaluated by the Dual-Luciferase reporter assay. Satb2 expression was detected by Western blot. The pcDNA-miR-1301 plasmid was transfected into BMSCs to upregulate the expression of miR-1301, which promoted cell proliferation, decreased Bax expression, and increased Bcl-2 expression and ALP activity. In addition, it also elevated the expression of RUNX2 and OPN and decreased the expression of FABP4, PPARγ2, and Satb2. Compared with the control group, the difference was statistically significant (p<0.05); Satb2 was the target gene of miR-1301. MiR-1301 siRNA transfected into BMSCs down-regulated miR-1301 expression, inhibited cell proliferation, increased Bax expression and decreased Bcl-2 expression and ALP activity. Meanwhile, miR-1301 siRNA also reduced RUNX2 and OPN expression and increased expression of FABP4, PPARγ2 and Satb2. The difference was statistically significant compared with control group (p<0.05). Regulation of miR-1301 expression in BMSCs can improve BMSCs proliferation and regulate their adipogenic and osteogenic differentiation by regulating Satb2.

From This Month's Histopathology

From This Month's Histopathology

Clinical, histopathologic, subtype, and immunohistochemical analysis of jaw phosphaturic mesenchymal tumors.

Jaw phosphaturic mesenchymal tumors (PMTs) are a rare neoplasm with uncertain histogenesis. This study aimed to clarify the clinical and pathological features of jaw PMTs.We reviewed the clinical records of 39 patients diagnosed with PMTs in the jaws, and investigated clinical and morphologic characteristics, histologic subtypes, and immunophenotypes of all cases.Microscopic analyses revealed 2 major histologic tumor subtypes: “phosphaturic mesenchymal tumors of mixed epithelial and connective tissue” (PMTMECT), and “phosphaturic mesenchymal tumors of mixed connective tissue” (PMTMCT). PMTMECTs and PMTMCTs accounted for 29 and 10 cases of PMTs, respectively. Most PMTMECT diagnoses were made predominantly in males aged <45 years, and the incidence was similar in both the mandible and maxilla. In contrast, patients with PMTMCTs are predominantly females aged ≥45 years, and all tumors were in the mandible. Histologically, PMTMECT had lower cellularity and a more elongated and spindled mesenchymal component with less elaborate intrinsic microvasculature than PMTMCT. Immunohistochemically, the epithelia of all PMTMECTs was immunoreactive for AE1/AE3. Other immunohistochemical staining of PMTMECTs revealed positive expression of vimentin, SATB2, ERG, CD99, Bcl-2, CD56, S-100, D2-40, CD68, SMA, and CD34 in either one or both components. Immunohistochemical staining of PMTMCTs was diffusely positive for vimentin and a varied ratio of positivity for SATB2, ERG, CD99, Bcl-2, CD56, S-100, D2-40, CD68, SMA, and CD34, but negative for AE1/AE3. Most patients were cured by complete resection, except 2 patients who had repeated recurrences, one of which also had multiple metastasis.Jaw PMT can be divided into 2 major histological subtypes. PMTMECTs are more common than are PMTMCTs, and can transform into malignant PMTMCTs during the progression. PMTMECTs were more commonly observed in males and the incidence was similar in both the maxilla and mandible. PMTMCTs were almost always observed in the mandible of females. Compared with PMTMCTs, PMTMECTs have an admixture of epithelial components with less prominent vasculature and lower cellularity. There were no statistically significant differences in the expression of immunohistochemical markers except AE1/AE3 between PMTMECTs and PMTMCTs. However, immunohistochemical markers have great significance for differentiating other mesenchymal tumors.

SATB2 protein expression by immunohistochemistry is a sensitive and specific marker of appendiceal and rectosigmoid well differentiated neuroendocrine tumours.

Neuroendocrine neoplasms (NNs) range from well to poorly differentiated and indolent to highly aggressive. The site of origin in metastatic NNs has therapeutic and prognostic implications. SATB2 is a transcriptional regulator involved in osteoblastic and neuronal differentiation and is a sensitive and specific marker of colorectal epithelium. This study aimed to evaluate the expression of SATB2 in NNs from various primary sites and its utility as a marker in determining the site of origin of these neoplasms. SATB2 immunohistochemistry was performed on 266 NNs, including lung small cell carcinomas (n=39) and carcinoids (n=30), bladder (n=21) and prostate (n=31) small cell carcinomas, and gastrointestinal (GI)/pancreatic NNs of various primary sites (n=145) consisting of well-differentiated neuroendocrine tumours (WDNET)s (n=124) and poorly differentiated neuroendocrine carcinomas (PDNEC)s (n=21). SATB2 was expressed in prostatic (10 of 31, 32%) and bladder (eight of 21, 38%) small cell carcinomas, lung carcinoid tumours (one of 30, 3%), and lung small cell carcinomas (eight of 39, 21%). Among primary GI NNs, SATB2 was expressed in 37 of 124 (30%) WDNETs and four of 21 (19%) PDNECs. Of the former, 15 of 15 (100%) rectal/rectosigmoid and 22 of 22 (100%) appendiceal neoplasms expressed SATB2. Using receiver operator characteristic analysis, SATB2 was a sensitive and specific marker for rectal (100.0%, 80.0%) and appendiceal (100.0%, 84.5%) WDNETs, respectively. In summary, SATB2 is a sensitive and specific marker for rectal/rectosigmoid and appendiceal WDNETs, and may represent a useful diagnostic tool when these sites of origin are considered in the differential diagnosis.

Traditional serrated adenoma-like lesions in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal carcinoma. The significance of serrated lesions resembling traditional serrated adenoma (TSA) in IBD patients is unclear. In this retrospective study, we analyzed 52 TSA-like lesions arising in 30 IBD patients and diagnosed in colectomy or endoscopic specimens. The 27 colectomy lesions presented predominantly as ill-defined areas with granular appearance, with a median size of 15 mm, located throughout the large bowel and associated with synchronous advanced colorectal lesions in 58%. Low-grade serrated dysplasia was present in 56%, high-grade serrated dysplasia in 37%, and TSA-type cytology in 7%. Increased Ki-67 immunostaining and abnormal p53 expression were identified in 96% and 48%, respectively; 74% had a KRAS mutation, and 4% had a BRAF mutation. Endoscopically resectable TSA-like lesions were all discrete polypoid lesions, smaller in size (median 9 mm), predominantly in the distal large bowel, with an adjacent precursor polyp in 24%, and associated with synchronous and metachronous advanced colorectal lesions in 6%. Most (92%) show TSA-type cytology. p53 overexpression was present in 4%, KRAS mutation in 41%, and BRAF mutation in 32%. None of the 52 TSA-like lesions demonstrated loss of MLH1 or SATB2 expression by immunohistochemistry. On follow-up, 4 patients were diagnosed with colorectal carcinoma or high-grade adenomatous IBD-associated dysplasia. None of the patients with lesions showing TSA-type cytology only developed an advanced lesion. Our findings suggest that some TSA-like lesions, essentially from colectomy, may represent a form of IBD-associated dysplasia associated with an increased risk of advanced neoplasia.

Xist noncoding RNA could act as a tumor suppressor gene in patients with classical Hodgkin's disease

Xist is a long noncoding RNA involved in the X chromosome inactivation in females. It may act as an onco-suppressor gene in hematologic malignancies, and its activity is strongly dependent from SATB1 gene expression. However, its potential role in Hodgkin's disease (HD) onset and progression is unknown. Three gene expression microarray datasets were analyzed for the expression of Xist and SATB1 in patients with classical HD, namely, GDS4222 (130 patients and 54,000 gene features), GSE39134 (29 patients and 54,000 features), and E-MEXP-507 (29 patients and 27,648 probes). The first two were oligonucleotide arrays (platform: Affymetrix gene chip HG-U133-Plus2), whereas the latter was a cDNA two-channel array (platform: OncoChip. v2). Summary and time-dependent receiver operating characteristic (ROC) analysis were applied to obtain a summary measure (summary area under the ROC curve [sAUC]) of association between gene expression and unfavorable patient outcome in each probe set. Xist was overexpressed among females in each data set. A slight overexpression was associated with a good prognosis both in males (sAUC = 0.75, 95% confidence interval [CI]: 0.70-0.80) and at a lesser extent, in females (sAUC = 0.64, 95% CI: 0.59-0.69). However, this finding was limited to the analysis of the biggest database (GDS4222). No association was found between Xist and SATB1 expression. A reactivation of Xist might act as an onco-suppressor gene in male patients with HD, which seems independent from SATB1 expression. The possibility that Xist could contribute to the better survival of female patients should also be investigated.

Maternal regulation of SATB2 in osteo-progeniters impairs skeletal development in offspring.

Nutritional status during intrauterine and/or early postnatal life has substantial influence on adult offspring health. Along these lines, there is a growing body of evidence illustrating that high fat diet (HFD)-induced maternal obesity can regulate fetal bone development. Thus, we investigated the effects of maternal obesity on both fetal skeletal development and mechanisms linking maternal obesity to osteoblast differentiation in offspring. Embryonic osteogenic calvarial cells (EOCCs) were isolated from fetuses at gestational day 18.5 (E18.5) of HFD-induced obese rat dams. We observed impaired differentiation of EOCCs to mature osteoblasts from HFD obese dams. ChIP-seq-based genome-wide localization of the repressive histone mark H3K27me3 (mediated via the polycomb histone methyltransferase, enhancer of zeste homologue 2 [Ezh2]) showed that this phenotype was associated with increased enrichment of H3K27me3 on the gene of SATB2, a critical transcription factor required for osteoblast differentiation. Knockdown of Ezh2 in EOCCs and ST2 cells increased SATB2 expression; while Ezh2 overexpression in EOCCs and ST2 cells decreased SATB2 expression. These data were consistent with experimental results showing strong association between H3K27me3, Ezh2, and SATB2 in cells from rats and humans. We have further presented that SATB2 mRNA and protein expression were increased in bones, and increased trabecular bone mass from pre-osteoblast specific Ezh2 deletion (Ezh2flox/flox Osx-Cre+ cko) mice compared with those from control Cre+ mice. These findings indicate that maternal HFD-induced obesity may be associated with decreasing fetal pre-osteoblastic cell differentiation, under epigenetic control of SATB2 expression via Ezh2-dependent mechanisms.

From This Month's Histopathology

From This Month's Histopathology

Dehydroandrographolide Inhibits Osteosarcoma Cell Growth and Metastasis by Targeting SATB2-mediated EMT.

The 12-hydroxy-14-dehydroandrographolide (DP) is a predominant component of the traditional herbal medicine Andrographis paniculata (Burm. f.) Nees (Acanthaceae). Recent studies have shown that DP exhibits potent anti-cancer effects against oral and colon cancer cells. This investigation examined the potential effects of DP against osteosarcoma cell. A cell analyzer was used to measure cell viability. The cell growth and proliferation were performed by Flow cytometry and BrdU incorporation assay. The cell migration and invasion were determined by wound healing and transwell assay. The expression of EMT related proteins was examined by Western blot analysis. In this study, we found that DP treatment repressed osteosarcoma (OS) cell growth in a dose-dependent manner. DP treatment significantly inhibited OS cell proliferation by arresting the cell cycle at G2/M phase. In addition, DP treatment effectively inhibited the migration and invasion abilities of OS cells through wound healing and Transwell tests. Mechanistic studies revealed that DP treatment effectively rescued the epithelialmesenchymal transition (EMT), while forced expression of SATB2 in OS cells markedly reversed the pharmacological effect of DP on EMT. Our data demonstrated that DP repressed OS cell growth through inhibition of proliferation and cell cycle arrest; DP also inhibited metastatic capability of OS cells through a reversal of EMT by targeting SATB2. These findings demonstrate DP's potential as a therapeutic drug for OS treatment.

A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases

Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7−/CK20+/CDX2+/PAX8−. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1–50% of tumor cells) and diffuse ( >50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker in distinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice.

Metastatic colorectal carcinomas with high SATB2 expression are associated with better prognosis and response to chemotherapy: a population-based Scandinavian study

Background: Survival and response to therapy in patients with metastatic colorectal cancer (mCRC) are very heterogeneous. There is an unmet need for better markers of prognosis and treatment benefit for mCRC patients. The homeobox 2 gene SATB2 has a highly specific expression in colorectal tissue and is associated with better prognosis in non-metastatic CRC.Material and methods: A population-based cohort of 798 mCRC patients was analysed. From primary tumour material, protein expression was assessed by immunohistochemistry. BRAF and KRAS mutation status was also determined. Associations with clinicopathological data, overall and progression-free survival and response to first-line chemotherapy were analysed.Results: Tumour tissue and clinical data were available from 467 patients. SATB2 was strongly expressed in 58% of cases, significantly more in left-sided, low-grade and wild-type BRAF tumours. Patients with high SATB2 tumours had longer overall survival compared with low SATB2 tumours (median 13 vs 8 months respectively, p < .001). Chemotherapy was given to 282 patients (63%). Patients with high SATB2 tumours had longer OS (median 22 vs 15 months respectively, p = .001) and more often responded to chemotherapy than those with low SATB2 (objective response 43% vs 29%, p = .02; clinical response 83% vs 67%, p = .004). Progression-free survival on first-line irinotecan chemotherapy was longer in high SATB2 cases (median 8 vs 4 months respectively, p = .019). Patients with both low SATB2 expression and mutated BRAF (n = 69) had particularly poor survival compared to the rest (median 8 and 12 months respectively, p = .001). In multivariable analysis, the SATB2 findings were independent of known clinicopathological prognostic markers, including BRAF mutation status.Conclusion: Patients with mCRC expressing high level of SATB2 have better prognosis and response to chemotherapy than those with low SATB2 expression. Patients with both low SATB2 expression and mutated BRAF had particularly poor prognosis and could thus benefit from more aggressive therapies.

Clinical and molecular characterization of primary sclerosing epithelioid fibrosarcoma of bone and review of the literature.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare sarcoma subtype characterized by monomorphic epithelioid cells embedded in a densely sclerotic collagenous matrix. The overwhelming majority of tumors arise in soft tissues; however, rare cases have been documented to occur primarily in bone. The hallmarks of soft tissue SEF include MUC4 immunoreactivity and the presence of an EWSR1-CREB3L1 fusion. Rare cases with alternative fusions have also been reported such as EWSR1-CREB3L2 and FUS-CREB3L2 transcripts. The molecular alterations of skeletal SEF have not been well-defined, with only rare cases analyzed to date. In this study we investigated the clinicopathologic and molecular features of seven patients presenting with primary osseous SEF. There were 3 males and 4 females, with a mean age at diagnosis of 38 years. All cases had microscopic features within the histologic spectrum of SEF and showed strong and diffuse MUC4 positivity, while lacking SATB2 expression. However, due to its unusual presentation within bone, four cases were initially misinterpreted as either osteosarcoma, Ewing sarcoma or chondroblastoma. Half of the patients with follow-up data developed metastasis. The cases were tested by targeted RNA sequencing, MSK-IMPACT, and/or fluorescence in situ hybridization, showing EWSR1-CREB3L1 in six cases and EWSR1-CREB3L2 in one case. The fusion transcripts were composed of EWSR1 exon 11 to either exon 6 of CREB3L1 or CREB3L2. In summary, due to their rarity in the bone, skeletal SEF are often misdiagnosed, resulting in inadequate treatment modalities. Similar to their soft tissue counterpart, bone SEF follow an aggressive clinical behavior and show similar EWSR1-CREB3L1/CREB3L2 fusions.

LncRNA MALAT1 shuttled by bone marrow-derived mesenchymal stem cells-secreted exosomes alleviates osteoporosis through mediating microRNA-34c/SATB2 axis.

Long non-coding RNAs (lncRNAs) have emerged as promising novel modulators during osteogenesis in mesenchymal stem cells (MSCs). Enhanced SATB2 has been demonstrated to promote osteogenic differentiation of bone marrow-derived mesenchymal stem cells (hBMSCs) in patients with osteonecrosis. Preliminary bioinformatic analysis identified putative binding sites between microRNA-34c (miR-34c) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) or miR-34c and SATB2 3’UTR. Thus, the current study aimed to clarify the potential functional relevance of MALAT1-containing exosomes from BMSCs in osteoporosis. The extracted exosomes from primary BMSCs were co-cultured with human osteoblasts (hFOB1.19), followed by evaluation of the hFOB1.19 cell proliferation, alkaline phosphatase (ALP) activity and mineralized nodules. The obtained findings indicated that BMSC-Exos promoted the expression of SATB2 in osteoblasts, and SATB2 silencing reduced the ALP activity of osteoblasts and mineralized nodules. MALAT1 acted as a sponge of miR-34c to promote the expression of SATB2. Additionally, BMSCs-derived exosomal MALAT1 promoted osteoblast activity. Moreover, in vivo experiments indicated that miR-34c reversed the effect of MALAT1, and SATB2 reversed the effect of miR-34c in ovariectomized mice. Taken together, this study demonstrates that BMSCs-derived exosomal MALAT1 enhances osteoblast activity in osteoporotic mice by mediating the miR-34c/SATB2 axis.

HER2, NF-κB, and SATB1 Expression Patterns in Gastric Cancer and Their Correlation with Clinical and Pathological Parameters.

Gastric cancer (GC) is currently recognized as one of the most common and fatal tumor worldwide. The identification of novel biomarkers in relation to clinical information as well as extending the knowledge on a multiple crosstalk between various oncogenic pathways implicated in GC carcinogenesis seems pivotal to limit the disease-associated mortality. Therefore, we assessed the expression of HER2, NF-κB, and SATB1 in a total of 104 gastric adenocarcinomas and 30 normal gastric samples and correlated the expression patterns with each other and with some clinicopathological variables. Protein expression was examined by immunohistochemistry (IHC) on tissue microarrays (TMAs), and fluorescence in situ hybridization (FISH) was employed to detect HER2 amplification. In the studied group, HER2 and SATB1 were found to be overexpressed in gastric cancer tissue in comparison to normal gastric mucosa. The expression status of the former protein was seen to differ according to some clinicopathological features, but without statistical significance, whereas the expression of the latter was not importantly associated with any of them. In turn, the NF-κB protein level was significantly related to the presence of lymph node metastasis. HER2 expression was not significantly correlated with that of other proteins, but a positive correlation was found between the expression of SATB1 and NF-κB. Further studies with a larger group of patients combined with in vitro mechanistic experiments are required to fully elucidate the role and relationship of HER2, NF-κB, and SATB1 expression in gastric cancer progression. However, to the best of our knowledge, this study is the first look at a simultaneous evaluation of these three markers in the samples of gastric cancer patients.

Higher expression of SATB2 in hepatocellular carcinoma of African Americans determines more aggressive phenotypes than those of Caucasian Americans.

In the United States, Hepatocellular Carcinoma (HCC) incidence has tripled over the past two decades. The disease has disproportionately affected minority and disadvantaged populations. The purpose of this study was to examine the expression of SATB2 gene in HCC cells derived from African Americans (AA) and Caucasian Americans (CA) and assess its oncogenic potential by measuring cell viability, spheroid formation, epithelial‐mesenchymal transition (EMT), stem cell markers and pluripotency maintaining factors in cancer stem cells (CSCs). We compared the expression of SATB2 in human primary hepatocytes, HCC cells derived from AA and CA, and HCC CSCs. Hepatocellular carcinoma cells derived from AA expressed the higher level of SATB2 than those from CA. By comparison, normal human hepatocytes did not express SATB2. Higher expression of SATB2 in HCC cells from AA was associated with greater growth rate, cell viability, colony formation and EMT characteristics than those from CA. Knockout of SATB2 in CSCs by Crispr/Cas9 technique significantly inhibited the expression of SATB2 gene, stem cell markers (CD24, CD44 and CD133), pluripotency maintaining factors (c‐Myc, KLF4, SOX2 and OCT4), and EMT compared with non‐targeting control group. The expression of SATB2 was negatively correlated with miR34a. SATB2 rescued the miR‐34a‐mediated inhibition of CSC's viability. These data suggest that SATB2 is an oncogenic factor, and its higher expression may explain the disparity in HCC outcomes among AA.

Long noncoding RNA DRAIC acts as a microRNA-122 sponge to facilitate nasopharyngeal carcinoma cell proliferation, migration and invasion via regulating SATB1

Increasing evidences have revealed that long noncoding RNAs (lncRNAs) are frequently involved in various cancers. However, the expression and function of lncRNA DRAIC in nasopharyngeal carcinoma (NPC) remain unknown. In this study, we found that DRAIC was significantly increased in NPC tissues. Increased expression of DRAIC was positively correlated with advanced clinical stages of NPC patients. Functional assays revealed that ectopic expression of DRAIC enhances NPC cell growth, migration and invasion. DRAIC knockdown represses NPC cell growth, migration and invasion. Mechanistically, we identified two miR-122 binding sites on DRAIC. RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assays confirmed the binding of DRAIC to miR-122. Via binding of miR-122, DRAIC upregulated the expression of miR-122 target SATB1, which was abolished by the mutation of miR-122 binding sites on SATB1. Moreover, the oncogenic roles of DRAIC on NPC were reversed by the mutation of miR-122 binding sites on SATB1, simultaneous overexpression of miR-122, or depletion of SATB1. In addition, the expression of SATB1 was also increased and positively associated with that of DRAIC in NPC tissues. In conclusion, these findings revealed the important roles of DRAIC-miR-122-SATB1 axis in NPC and suggested that DRAIC may be a potential therapeutic target for NPC.