A possible pattern in the evolution of male meiotic cytokinesis in angiosperms.

Evolution of cellular characteristics is a fundamental aspect of evolutionary biology, but knowledge about evolution at the cellular level is very limited. In particular, whether a certain intracellular characteristic evolved in angiosperms, and what significance of such evolution is to angiosperms, if it exists, are important and yet unanswered questions. We have found that bidirectional cytokinesis occurs or likely occurs in male meiosis in extant basal and near-basal angiosperm lineages, which differs from the unidirectional cytokinesis in male meiosis in monocots and eudicots. This pattern of cytokinesis in angiosperms seems to align with the distribution pattern of angiosperms with the lineages basal to monocots and eudicots living in tropical, subtropical or temperate environments and monocots and eudicots in an expanded range of environments including tropical, subtropical, temperate, subarctic and arctic environments. These two cytokinetic modes seem to result from two phragmoplast types, respectively. A phragmoplast in the bidirectional cytokinesis dynamically associates with the leading edge of a growing cell plate whereas a phragmoplast in the unidirectional cytokinesis is localized to an entire division plane. The large assembly of microtubules in the phragmoplast in unidirectional cytokinesis may be indicative of increased microtubule stability compared with that of the small microtubule assembly in the phragmoplast in bidirectional cytokinesis. Microtubules could conceivably increase their stability from evolutionary changes in tubulins and/or microtubule-associated proteins. Microtubules are very sensitive to low temperatures, which should be a reason for plants to be sensitive to low temperatures. If monocots and eudicots have more stable microtubules than other angiosperms, they will be expected to deal with low temperatures better than other angiosperms. Future investigations into the male meiotic cytokinetic directions, microtubule stability at low temperatures, and proteins affecting microtubule stability in more species may shed light on how plants evolved to inhabit cold environments.

Adjuvant therapy with Jianpi Huayu decoction improves overall and recurrence-free survival after hepatectomy for hepatocellular carcinoma: a retrospective propensity score-matching study.

Hepatocellular carcinoma (HCC) patients experience high rates of recurrence following hepatectomy. Many herbal preparations used in traditional Chinese medicine have been shown to improve the postoperative condition of cancer patients. This retrospective study examined the efficacy and safety of Jianpi Huayu decoction (JPHYD) as adjuvant therapy for HCC following hepatectomy. HCC patients received postoperative management according to Chinese Society of Clinical Oncology recommendations, either alone (Control group) or in addition to daily JPHYD (1 week in hospital and 3 months after release). To reduce selection bias, we performed 1:1 propensity score matching between the Control and JPHYD groups. The main endpoint was recurrence-free survival (RFS), and secondary endpoints included overall survival (OS) and adverse event frequency. A total of 207 patients meeting inclusion criteria were enrolled, 127 in the Control group and 80 in the JPHYD group. Patients were then propensity score-matched, yielding each group of 80. Recurrence-free survival rate was significantly higher in the JPHYD group than in the Control group at 1 year (67.9% vs. 38.1%), 2 years (39.1% vs. 26.2%), and 3 years (31.3% vs. 26.2%) following hepatectomy (HR 0.5666 [95%CI, 0.3655 to 0.8784]; p = 0.0066). Additionally, OS was significantly higher in the JPHYD group than the Control group at 1 year (94.3% vs. 81.9%), 2 years (76.4% vs. 58.8%), and 3 years (66.3% vs. 51.4%) following hepatectomy (HR 0.5199 [95%CI, 0.2849 to 0.9490]; p = 0.027). Adverse events frequencies did not differ between the two groups. In conclusion, JPHYD can safely improve RFS and OS following hepatectomy for HCC.

A novel indolylbenzoquinone compound HL-J6 suppresses biofilm formation and α-toxin secretion in methicillin-resistant Staphylococcus aureus.

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) is challenging due to multi-drug resistance of strains and biofilm formation, the latter of which is an important barrier to the penetration of antibiotics and host defences. As such, there is an urgent need to discover and develop novel agents to fight MRSA-associated infection. In this study, HL-J6, a novel indolylbenzoquinone compound, was shown to inhibit S. aureus strains, with a minimum inhibitory concentration against MRSA252 of 2 µg/mL. Moreover, HL-J6 exhibited potent antibiofilm activity in vitro and was able to kill bacteria in biofilm. In the mouse models of wound infection, HL-J6 treatment reduced the MRSA load significantly and inhibited biofilm formation on the wounds. The potent targets of its antibiofilm activity were explored by real-time reverse transcriptase polymerase chain rection, which indicated that HL-J6 downregulated the transcription levels of sarA, atlAE and icaADBC. Moreover, Western blot results showed that HL-J6 reduced the secretion level of α-toxin, a major virulence factor. These findings indicate that HL-J6 is a promising lead compound for the development of novel drugs against MRSA biofilm infections.

Transcriptional regulations of pollen tube reception are associated with the fertility of the ginger species Zingiber zerumbet and Zingiber corallinum.

Zingiber zerumbet and Zingiber corallinum are economically valuable species in the genus Zingiber. While Z. corallinum is sexually active, Z. zerumbet adopts clonal propagation, although it has the potential for sexual reproduction. It is unclear so far at which step during the sexual reproduction of Z. zerumbet inhibition occurs, and what are the regulatory mechanisms underlying this inhibition. Here, by comparing with the fertile species Z. corallinum using microscopy-based methods, we show that rare differences were observed in Z. zerumbet up to the point when the pollen tubes invaded the ovules. However, a significantly higher percentage of ovules still contained intact pollen tubes 24 h after pollination, suggesting pollen tube rupture was impaired in this species. Further RNA-seq analysis generated accordant results, showing that the transcription of ANX and FER, as well as genes for the partners in the same complexes (e.g., BUPS and LRE, respectively), and those putative peptide signals (e.g., RALF34), were timely activated in Z. corallinum, which ensured the pollen tubes being able to grow, reorient to ovules, and receipt by embryo sacs. In Z. zerumbet, genes for these complexes were cooperatively suppressed, which would result in the maintenance of PT integrity due to the disruption of RALF34-ANX/BUPS signaling in PT and the failure of PT reception by an active synergid due to the insufficiency of the synergid-harbored FER/LRE complex. Taking the results from the cytological and RNA-seq studies together, a model is proposed to illustrate the possible regulation mechanisms in Z. zerumbet and Z. corallinum, in which the regulations for pollen tube rupture and reception are proposed as the barrier for sexual reproduction in Z. zerumbet.

Transposable elements activation triggers necroptosis in mouse embryonic stem cells.

Deficiency of the histone H3K9 methyltransferase SETDB1 induces RIPK3-dependent necroptosis in mouse embryonic stem cells (mESCs). However, how necroptosis pathway is activated in this process remains elusive. Here we report that the reactivation of transposable elements (TEs) upon SETDB1 knockout is responsible for the RIPK3 regulation through both cis and trans mechanisms. IAPLTR2_Mm and MMERVK10c-int, both of which are suppressed by SETDB1-dependent H3K9me3, act as enhancer-like cis-regulatory elements and their RIPK3 nearby members enhance RIPK3 expression when SETDB1 is knockout. Moreover, reactivated endogenous retroviruses generate excessive viral mimicry, which promotes necroptosis mainly through Z-DNA-binding protein 1 (ZBP1). These results indicate TEs play an important role in regulating necroptosis.

Regioselective C-H chalcogenylation and halogenation of arenes and alkenes under metal-free conditions.

The reactions of direct Csp2-H chalcogenylation and halogenation of N-arylpyrrolidone under the action of PIFA without a directing group and under metal-free conditions were reported in this paper. Diphenyl selenide/sulfur and selenium phenyl halides were used as reaction reagents to obtain chalcogenylated and halogenated N-arylpyrrolidone products, respectively. The mechanistic studies indicated that a radical pathway was likely involved in these reactions. Preliminary antitumor tests showed that these compounds have moderate to potent activities against human acute leukemia cells K562 in vitro, which may be used as lead compounds for subsequent research.

Intrahepatic activated leukocyte cell adhesion molecule induces CD6highCD4+ T cell infiltration in autoimmune hepatitis.

Background and objectives: Autoimmune hepatitis (AIH) is characterized by the expansion and accumulation of pathogenic T cells in liver. Although CD6 and its ligand activated leukocyte cell adhesion molecule (ALCAM) are involved in the evolution of multiple inflammatory diseases, their roles in the pathogenesis of AIH remain unknown. Herein, we aimed to investigate ALCAM-CD6 axis in AIH development. Methods: Immunohistochemistry was performed to examine hepatic expression of CD6 and ALCAM. The concentration of serum ALCAM was evaluated by ELISA. The phenotypes of liver infiltrating T cells were determined by flow cytometry. Primary human CD4+ T cells were used for functional studies. Results: Our data showed that patients with AIH exhibited significantly higher expression of CD6 in the liver as compared to primary biliary cholangitis (PBC), chronic hepatitis B (CHB), non-alcoholic liver disease (NAFLD), and healthy controls (HC). In addition, hepatic CD6 expression was strongly correlated with disease severity of AIH. CD6 was mainly expressed on CD4+ T cells in the liver and intrahepatic CD6highCD4+ T cells demonstrated stronger proinflammatory response and proliferation features than CD6low counterparts in both AIH and HC. ALCAM, the ligand of CD6, was highly expressed in the hepatocytes of AIH and serum ALCAM was strongly associated with clinical indices of AIH. Interestingly, close spatial location between CD6+CD4+ T cells and ALCAM+ hepatocytes was observed. Finally, we found that CD6highCD4+ T cells showed enhanced capacity of trans-endothelial migration in vitro, which could be promoted by recombinant ALCAM. Conclusions: Our study found that ALCAM-CD6 axis was upregulated in the AIH liver, suggesting a potential target for alleviating AIH.

Synthesis and antitumor activity of a series of novel N-aryl-5-(2,2,2-trifluoroethoxy)-1,5-dihydro-2H-pyrrol-2-ones derivatives.

With the help of the establishment of novel reaction methodology, a series of N-Aryl-5-(2,2,2-trifluoroethoxy)-1,5-dihydro-2H-pyrrol-2-one conjugates were designed and synthesized in 2-4 steps, and subsequent anticancer activity of these compounds was evaluated. Preliminary results showed that these compounds have moderate to potent activities against human acute leukemia cells K562, human lung cancer A549, human breast cancer MDA-MB-231, and human cervical cancer HeLa cancer cell lines. Among them, compounds 2d and 2k were the most potent against K562 cell line with IC50 values of 0.07 and 0.52 µM, respectively, and the toxicity of 2d to the normal of hepatocytes (LO2) cell line was low (the survival rate 81 %). Flow cytometry analysis showed that 2d arrested K562 cells in the G2/M phase potently, even much better than Combretastatin A4 (CA4). In addition, the results demonstrated the involvement of the caspase-dependent or independent pathways of apoptosis, evidenced by the upregulation of FADD, pro-caspase 3, cleaved-caspase 3, HTRA2/Omi, SMAC/Diablo and the ratio of Bax/Bcl-2.The biological effects founding of 2d in this work point to prospective uses against acute leukemia.

Serum Biomarkers for Autoimmune Hepatitis Type 1: the Case for CD48 and a Review of the Literature.

In autoimmune hepatitis (AIH), the persisting inflammation contributes to fibrosis progression, for which conventional biochemical markers manifest relatively unsatisfactory prediction. Herein, we assessed the value of serum CD48 (sCD48) as an indicator for inflammation and fibrosis in AIH type 1. The levels of sCD48 were detected first in an exploratory cohort using ELISA. In this cohort, compared with healthy controls (4.90 ng/mL, P < 0.0001), primary biliary cholangitis (7.32 ng/mL, P < 0.0001), and non-alcoholic fatty liver disease (7.76 ng/mL, P < 0.0001), sCD48 levels were elevated in AIH (12.81 ng/mL) and correlated with histological inflammation and fibrosis. Further using multivariate logistic regression analysis, sCD48 was identified as an independent predictor for both significant inflammation (G3-4) and advanced fibrosis (S3-4). Two predictive scores, based on sCD48, were constructed for diagnosing significant inflammation and advanced fibrosis (sCD48-AIH-SI and sCD48-AIH-AF, respectively). Using these data as a premise, predictive abilities were subsequently evaluated and verified in a validation cohort. In the exploratory cohort, the area under the receiver operating characteristic curve of sCD48 and sCD48-AIH-SI, for significant inflammation, were 0.748 and 0.813, respectively. Besides, during treatment follow-up, sCD48 levels gradually decreased from immunosuppression initiation to re-evaluation biopsy, in parallel with aspartate transaminase, total sera IgG, and fibrosis-4 score. For AIH patients in a re-evaluation biopsy cohort, sCD48 could predict significant fibrosis (S2-4). Further using immunohistochemistry, hepatic CD48 expression was elevated in AIH patients and decreased after treatment. In conclusion, sCD48 and sCD48-based predictive scores predict histological inflammation and fibrosis in AIH-1. Detecting sCD48 might help in the clinical management of AIH.

Phosphorylation-dependent association of human chromatin protein PC4 to linker histone H1 regulates genome organization and transcription.

Human Positive Coactivator 4 (PC4) is a multifaceted chromatin protein involved in diverse cellular processes including genome organization, transcription regulation, replication, DNA repair and autophagy. PC4 exists as a phospho-protein in cells which impinges on its acetylation by p300 and thereby affects its transcriptional co-activator functions via double-stranded DNA binding. Despite the inhibitory effects, the abundance of phosphorylated PC4 in cells intrigued us to investigate its role in chromatin functions in a basal state of the cell. We found that casein kinase-II (CKII)-mediated phosphorylation of PC4 is critical for its interaction with linker histone H1. By employing analytical ultracentrifugation and electron microscopy imaging of in vitro reconstituted nucleosomal array, we observed that phospho-mimic (PM) PC4 displays a superior chromatin condensation potential in conjunction with linker histone H1. ATAC-sequencing further unveiled the role of PC4 phosphorylation to be critical in inducing chromatin compaction of a wide array of coding and non-coding genes in vivo. Concordantly, phospho-PC4 mediated changes in chromatin accessibility led to gene repression and affected global histone modifications. We propose that the abundance of PC4 in its phosphorylated state contributes to genome compaction contrary to its co-activator function in driving several cellular processes like gene transcription and autophagy.

Design, synthesis, and evaluation of a novel series of mono-indolylbenzoquinones derivatives for the potential treatment of breast cancer.

Breast cancer is one of the most common cancers in the world, and pro-apototic drugs activating the apoptotic pathway are a strategy for anticancer therapy. To explore new antineoplastic agents, a series of novel mono-indolylbenzoquinone derivatives have been designed and synthesized. Compared with the lead bis-indolylbenzoquinones, most of the novel mono-indolylbenzoquinone derivatives have significantly increased their activity against A549, HeLa, and especially, MDA-MB-231 cell lines. Among them, 10d has the lowest IC50 value of 70 nM on MDA-MB-231 cells. Moreover, its oral toxicity is extremely low with an LD50 value of 374 mg/kg and no obvious liver and kidney damage to mice. 10d down-regulated Bcl-2, up-regulated Bax, and increased the release of cytochrome C, caspase3 and 9. 10d also up-regulated the expression of p53, catalase, and HTRA2/Omi. Therefore, 10d may exert its anticancer activity by activating apoptotic pathway and p53 expression. In vivo, 10d suppressed breast cancer 4T1 tumor growth with 36% inhibition ratio of tumor by intraperitoneal injection in mice. Furthermore, a cross-linked cyanoacrylate (CA)-based local sustained-release drug delivery systems (LSRDDSs) improved 10d anticancer activity to 49.8% inhibition of tumor growth. Taken together, 10d could be a promising drug candidate for clinical development to treat metastatic breast cancer.

Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquitination and degradation of CENP-A during the cell cycle.

CENP-A (centromeric protein A), a histone H3 variant, specifies centromere identity and is essential to centromere maintenance. Little is known about how protein levels of CENP-A are controlled in mammalian cells. Here, we report that the phosphorylation of CENP-A Ser68 primes the ubiquitin-proteasome-mediated proteolysis of CENP-A during mitotic phase in human cultured cells. We identify two major polyubiquitination sites that are responsible for this phosphorylation-dependent degradation. Substituting the two residues, Lys49 and Lys124, with arginines abrogates proper CENP-A degradation and results in CENP-A mislocalization to non-centromeric regions. Furthermore, we find that DCAF11 (DDB1 and CUL4 associated factor 11/WDR23) is the E3 ligase that specifically mediates the observed polyubiquitination. Deletion of DCAF11 hampers CENP-A degradation and causes its mislocalization. We conclude that the Ser68 phosphorylation plays an important role in regulating cellular CENP-A homeostasis via DCAF11-mediated degradation to prevent ectopic localization of CENP-A during the cell cycle.

Phase separation drives the self-assembly of mitochondrial nucleoids for transcriptional modulation.

Mitochondria, the only semiautonomous organelles in mammalian cells, possess a circular, double-stranded genome termed mitochondrial DNA (mtDNA). While nuclear genomic DNA compaction, chromatin compartmentalization and transcription are known to be regulated by phase separation, how the mitochondrial nucleoid, a highly compacted spherical suborganelle, is assembled and functions is unknown. Here we assembled mitochondrial nucleoids in vitro and show that mitochondrial transcription factor A (TFAM) undergoes phase separation with mtDNA to drive nucleoid self-assembly. Moreover, nucleoid droplet formation promotes recruitment of the transcription machinery via a special, co-phase separation that concentrates transcription initiation, elongation and termination factors, and retains substrates to facilitate mtDNA transcription. We propose a model of mitochondrial nucleoid self-assembly driven by phase separation, and a pattern of co-phase separation involved in mitochondrial transcriptional regulation, which orchestrates the roles of TFAM in both mitochondrial nucleoid organization and transcription.

Nymphaea colorata, another basal angiosperm species with bidirectional cytokinesis in microsporogenesis.

Comparing cellular features in microsporogenesis across taxa may yield important clues to evolution of meiosis in plants. We previously provided evidence that bidirectional cytokinesis occurs in M. denudata and suggested that the same may also occur in P. trimera based on a published report. Both M. denudata and P. trimera are basal angiosperm species that belong to the order of Magnoliales. For comparison, only unidirectional cytokinesis, either centripetal or centrifugal cytokinesis, has been found in microsporogenesis in eudicots and monocots. These observations raise the possibility that bidirectional cytokinesis is a common feature of microsporogenesis in basal angiosperms but not in eudicots and monocots. In this report, we provide evidence that bidirectional cytokinesis also occurs in another basal angiosperm species, Nymphaea colorata. The new findings, together with the previous findings, indicate that bidirectional cytokinesis is a prominent feature of microsporogenesis in at least some basal angiosperm species, and it occurs independently of cytokinesis types with respect to the timing of cytokinesis and tetrad configurations.

Cell polarity, asynchronous nuclear divisions, and bidirectional cytokinesis in male meiosis in Magnolia denudata.

Magnolia, a basal angiosperm genus important for evolutionary and phylogenetic studies, is known to have male meiotic features not seen in the vast majority of angiosperms. However, knowledge about male meiosis in Magnolia is still fragmentary. Here, we report findings from an extensive investigation into male meiosis in Magnolia denudata using a combination of light and electron microscopy methods. Male meiosis in M. denudata was synchronous in prophase I but asynchronous in subsequent nuclear divisions. The polarized microspore mother cells from late prophase I onward had an elongated cell shape and thickened callose wall areas at the two smaller ends of the cell. The first nuclear division occurred along the long axis of the cell and the first callose furrow formed at the equatorial plane of the first nuclear division at the late telophase I stage. The second equatorial callose furrow formed after telophase II in a plane perpendicular to the first callose furrow. While cytokinesis occurred centripetally from the two furrows, a central callose wall island (CWI) appeared in the center of the cell and dense assemblies of vesicles and short tubules decorated the cytoplasmic regions between the furrows and the CWI. This cytokinesis mode differs from either the centripetal or the centrifugal mode of cytokinesis in microsporogenesis in the vast majority of angiosperms. As a result of this unusual cytokinesis, a large central callose mass remains in the mature tetrads. These observations may be useful to studies of cytokinetic mechanisms, evolution of microsporogenesis, and phylogenetics of angiosperms.

Rett syndrome-causing mutations compromise MeCP2-mediated liquid-liquid phase separation of chromatin.

Rett syndrome (RTT), a severe postnatal neurodevelopmental disorder, is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). MeCP2 is a chromatin organizer regulating gene expression. RTT-causing mutations have been shown to affect this function. However, the mechanism by which MeCP2 organizes chromatin is unclear. In this study, we found that MeCP2 can induce compaction and liquid-liquid phase separation of nucleosomal arrays in vitro, and DNA methylation further enhances formation of chromatin condensates by MeCP2. Interestingly, RTT-causing mutations compromise MeCP2-mediated chromatin phase separation, while benign variants have little effect on this process. Moreover, MeCP2 competes with linker histone H1 to form mutually exclusive chromatin condensates in vitro and distinct heterochromatin foci in vivo. RTT-causing mutations reduce or even abolish the ability of MeCP2 to compete with histone H1 and to form chromatin condensates. Together, our results identify a novel mechanism by which phase separation underlies MeCP2-mediated heterochromatin formation and reveal the potential link between this process and the pathology of RTT.

Role of miR­34 in gastric cancer: From bench to bedside (Review).

Gastric cancer (GC) is a prevalent digestive system malignancy that is associated with a poor prognosis specifically for advanced­stage patients. MicroRNAs (miRNAs) are small, non­coding RNAs that have been reported to play roles as oncogenes or tumour suppressors in all types of cancer, including GC, by post­transcriptionally regulating cancer­related genes. Recently, miR­34a and miR­34b/c, members of the microRNA­34 (miR­34) family, were identified to be direct transcriptional targets of the onco­suppressor p53. In this review, we report that miR­34 is epigenetically downregulated or silenced in GC tissues and cell lines, changes which may result from mutations in p53 or DNA methylation and histone modifications of the miR­34 promoter regions. Moreover, miR­34 has been identified as a tumour­suppressor in GC. p53­induced miR­34 regulates several different target genes and signalling pathways, inducing apoptosis, senescence, and cell cycle arrest and repressing GC cell proliferation, migration and metastasis, thus contributing to the suppression of carcinogenesis and GC cancer progression. Furthermore, miR­34 is a novel prognostic and predictive biomarker in GC, and restoring miR­34 expression by delivering miR­34 mimics may be a promising therapeutic strategy for the treatment of GC.

MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review).

Gastric carcinogenesis arises from complicated interactions among host, environmental and bacterial factors, which cause genetic and epigenetic dysregulation of oncogenic and tumor­suppressive genes. MicroRNAs (miRNAs), a class of small non­coding RNAs that post­transcriptionally regulate ~30% human genes, may serve as oncogenes or tumor­suppressors in malignancies, including gastric cancer (GC). Although miRNA dysregulation commonly exists in GC, exact roles miRNAs serve in the pathogenesis and promotion of this tumor remain undetermined. Recently, results of previous studies regarding mechanisms underlying miRNAs generally converged on pathways critical in cellular processes, including cell proliferation, apoptosis and invasion, among which phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3­kinase (PI3K)/protein kinase B (Akt) signaling is a fundamental one, with frequent oncogenic alterations in GC. Therefore, in the present review, the disorder and function of miRNAs and PTEN/PI3K/Akt signaling in GC are discussed. Additionally, how miRNAs transduce their effects by regulating this pathway, particularly in GC stem cells and the tumor microenvironment, and two novel hypotheses significant in carcinogenesis, tumor progression and recurrence, are discussed. Furthermore, the roles of miRNAs and the PTEN/PI3K/Akt pathway in target therapies against this lethal disease are outlined.

Novel role of microRNA-126 in digestive system cancers: From bench to bedside.

MicroRNAs (miRNAs) are ubiquitously expressed, small, non-coding RNAs that regulate the expression of approximately 30% of the human genes at the post-transcriptional level. miRNAs have emerged as crucial modulators in the initiation and progression of various diseases, including numerous cancer types. The high incidence rate of cancer and the large number of cancer-associated cases of mortality are mostly due to a lack of effective treatments and biomarkers for early diagnosis. Therefore there is an urgent requirement to further understand the underlying mechanisms of tumorigenesis. MicroRNA-126 (miR-126) is significantly downregulated in a number of tumor types and is commonly identified as a tumor suppressor in digestive system cancers (DSCs). miR-126 downregulates various oncogenes, including disintegrin and metalloproteinase domain-containing protein 9, v-crk sarcoma virus CT10 oncogene homolog and phosphoinositide-3-kinase regulatory subunit 2. These genes are involved in a number of tumor-associated signaling pathways, including angiogenesis, epithelial-mensenchymal transition and metastasis pathways. The aim of the current review was to summarize the role of miR-126 in DSCs, in terms of its dysregulation, target genes and associated signaling pathways. In addition, the current review has discussed the potential clinical application of miR-126 as a biomarker and therapeutic target for DSCs.