Influência da via hippo no reparo da mucosite oral quimicamente induzida em modelo murino submetida a tratamento com laser, geleia real ou própolis / Influence of the hippo pathway on the repair of chemically induced oral mucositis in a murine model subjected to treatment with laser, royal jelly or propolis

A via hippo é uma via de transdução de sinal altamente conservada que está implicada no desenvolvimento, homeostase e regeneração celular/tecidual. A YAP tem papel fundamental na via hippo uma vez que junto com a TAZ ativam fatores de transcrição que levam ao crescimento, diferenciação e migração celular. O mecanismo de fosforilação da YAP/TAZ pela LATS1/LATS2 cria um sítio de ligação para manter a YAP no citoplasma (fosforilada) impedindo suas funções a nível nuclear. Diante das importantes funções desta via no reparo e crescimento tecidual, esta pesquisa avaliou se a via hippo exerceu influência na resposta ao tratamento da MO através da expressão das proteínas YAP e LATS2 em mucosite oral (MO) quimicamente induzida pelo 5- fluoracil (5-FU), em modelo murino, tratada com própolis (P), geleia real (GR) ou laser (L) comparadas ao grupo controle (C), sem tratamento. Foram utilizadas amostras de ratos machos wistar divididos nos seguintes grupos: C, P, GR e L (intraoral 6 J/cm2 ) separados em três tempos experimentais: dias 08, 10 e 14. O perfil de imunomarcação foi feito por escores padronizados entre 0 a 3 levando em consideração a marcação nuclear e/ou citoplasmática. Na análise de imunomarcação da YAP, no dia 08, o grupo controle obteve os escore 0 e 1 na maioria das amostras, já nos dias 10 e 14 a maior parte das amostras obteve os escore 2 e 3. Nos grupos experimentais (L, GR e P), o escore 2 prevaleceu em todos os tempos experimentais. Para LATS2 houve prevalência do escore 2 tanto no grupo controle quanto nos grupos teste em todos os tempos experimentais. Em relação a análise estatística da imunoexpressão da proteína YAP, verificou-se diferença estatítica significativa (p= 0,020), apenas no dia 08 entre o grupo controle comparado aos grupos experimentais (L, GR e P). Já para LATS2 nenhuma diferença estatística foi encontrada. Na avaliação estatística dos diferentes tempos experimentais dentro um mesmo grupo, só foi encontrada diferença estatística significativa no grupo laser e apenas para LATS2 (p=0,025). Adicionalmente foi realizada a correlação de spearman, entre YAP e LATS2 para todos os grupos, porém não houve associação estatística significativa. A maior imunoexpressão de YAP e LATS2 (escores 2 e 3) observada nos grupos experimentais, indica que a via hippo é ativada e parece influenciar o processo de reparo nas mucosites orais quimioinduzidas e tratadas pelos diferentes métodos (AU).

The hippo pathway is a highly conserved signal transduction pathway that is implicated in cell/tissue development, homeostasis and regeneration. YAP plays a key role in the hippo pathway since, together with TAZ, they activate transcription factors that lead to cell growth, differentiation and migration. The YAP/TAZ phosphorylation mechanism by LATS1/LATS2 creates a binding site to keep YAP in the cytoplasm (phosphorylated) preventing its functions at the nuclear level. Given the important functions of this pathway in tissue repair and growth, this research evaluated whether the hippo pathway exerted influence on the response to OM treatment through the expression of YAP and LATS2 proteins in oral mucositis (OM) chemically induced by 5-fluororacil (5- FU), in a murine model, treated with propolis (P), royal jelly (GR) or laser (L) compared to the control group (C), without treatment. Samples of male Wistar rats divided into the following groups were used: C, P, GR and L (intraoral 6 J/cm2) separated into three experimental times: days 08, 10 and 14. The immunostaining profile was performed by standardized scores between 0 to 3 taking into account nuclear and/or cytoplasmic labeling. In the YAP immunostaining analysis, on day 08, the control group obtained scores 0 and 1 in most samples, while on days 10 and 14 most samples obtained scores 2 and 3. In the experimental groups (L, GR and P), score 2 prevailed at all experimental times. For LATS2 there was a prevalence of score 2 both in the control group and in the test groups at all experimental times, showing a very heterogeneous expression. Regarding the statistical analysis of YAP protein immunoexpression, there was a statistically significant difference (p= 0.020), only on day 08 between the control group compared to the experimental groups (L, GR and P). As for LATS2, no statistical difference was found. In the statistical evaluation of the different experimental times within the same group, a statistically significant difference was only found in the laser group and only for LATS2 (p=0.025). Additionally, the Spearman correlation was performed between YAP and LATS2 for all groups, but there was no statistically significant association. The greater immunoexpression of YAP and LATS2 (scores 2 and 3) observed in the experimental groups indicates that the hippo pathway is activated and seems to influence the repair process in chemoinduced oral mucositis treated by different methods (AU).

Hippo-YAP signaling pathway regulates autophagy of human periodontal ligament cells under cyclic tensile stress / 华西口腔医学杂志

OBJECTIVES@#This work aimed to investigate the molecular mechanism of cyclic tensile stress (CTS) stimulating autophagy in human periodontal ligament cells (hPDLCs).@*METHODS@#hPDLCs were isolated and cultured from normal periodontal tissues. hPDLCs were loaded with tensile stress by force four-point bending extender to simulate the autophagy of hPDLCs induced by orthodontic force du-ring orthodontic tooth movement. XMU-MP-1 was used to inhibit the Hippo signaling pathway to explore the role of the Hippo-YAP signaling pathway in activating hPDLC autophagy by tensile stress. The expression levels of autophagy-related genes (Beclin-1, LC3, and p62) in hPDLCs were detected by real-time quantitative polymerase chain reaction. Western blot was used to detect the expression levels of autophagy-related proteins (Beclin-1, LC3-Ⅱ/LC3-Ⅰ, and p62) and Hippo-YAP pathway proteins (active-YAP and p-YAP) in hPDLCs. Immunofluorescence was used to locate autophagy-related proteins (LC3-Ⅱand p62) and Hippo-YAP pathway proteins (active-YAP) of hPDLCs.@*RESULTS@#CTS-activated autophagy in hPDLCs and expression of autophagy-related proteins initially increased and then decreased; it began to increase at 30 min, peaked at 3 h, and decreased (P<0.05). CTS increased the expression of active-YAP protein and decreased the expression of p-YAP protein (P<0.05). When XMU-MP-1 inhibited the Hippo-YAP signaling pathway (P<0.05), active-YAP protein was promoted to enter the nucleus and autophagy expression was enhanced (P<0.05).@*CONCLUSIONS@#The Hippo-YAP signaling pathway is involved in the regulation of autophagy activation in hPDLCs under CTS.

Reverse effect of Semaphorin-3F on rituximab resistance in diffuse large B-cell lymphoma via the Hippo pathway / 中华医学杂志(英文版)

BACKGROUND@#Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL.@*METHODS@#The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens.@*RESULTS@#We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo .@*CONCLUSION@#Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells / 中华肿瘤杂志

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.

Radix Scrophulariae Extracts Exert Effect on Hyperthyroidism via MST1/Hippo Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the mechanism of Radix Scrophulariae (RS) extracts in the treatment of hyperthyroidism rats by regulating proliferation, apoptosis, and autophagy of thyroid cell through the mammalian sterile 20-like kinase 1 (MST1)/Hippo pathway.@*METHODS@#Twenty-four rats were randomly divided into 4 groups according to a random number table: control, model group, RS, and RS+Hippo inhibitor (XMU-MP-1) groups (n=6 per group). Rats were gavaged with levothyroxine sodium tablet suspension (LST, 8 μ g/kg) for 21 days except for the control group. Afterwards, rats in the RS group were gavaged with RS extracts at the dose of 1,350 mg/kg, and rats in the RS+XMU-MP-1 group were gavaged with 1,350 mg/kg RS extracts and 1 mg/kg XMU-MP-1. After 15 days of administration, thyroid gland was taken for gross observation, and histopathological changes were observed by hematoxylin-eosin staining. The structure of Golgi secretory vesicles in thyroid tissues was observed by transmission electron microscopy. The expression of thyrotropin receptor (TSH-R) was observed by immunohistochemistry. Terminal-deoxynucleoitidyl transferase mediated nick end labeling assay was used to detect cell apoptosis in thyroid tissues. Real-time quantity primer chain reaction and Western blot were used to detect the expressions of MST1, p-large tumor suppressor gene 1 (LATS1), p-Yes1 associated transcriptional regulator (YAP), proliferating cell nuclear antigen (PCNA), G1/S-specific cyclin-D1 (Cyclin D1), B-cell lymphoma-2 (Bcl-2), Caspase-3, microtubule-associated proeins light chain 3 II/I (LC3-II/I), and recombinant human autophagy related 5 (ATG5). Thyroxine (T4) level was detected by enzyme-linked immunosorbent assay.@*RESULTS@#The thyroid volume of rats in the model group was significantly increased compared to the normal control group (P<0.01), and pathological changes such as uneven size of follicular epithelial cells, disorderly arrangement, and irregular morphology occurred. The secretion of small vesicles by Golgi apparatus was reduced, and the expressions of receptor protein TSH-R and T4 were significantly increased (P<0.01), while the expressions of MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 were significantly decreased (P<0.01). The expressions of Bcl-2, PCNA, and cyclin D1 were significantly increased (P<0.01). Compared with the model group, RS extracts reduced the volume of thyroid gland, improved pathological condition of the thyroid gland, promoted secretion of the secretory vesicles with double-layer membrane structure in thyroid Golgi, significantly inhibited the expression of TSH-R and T4 levels (P<0.01), upregulated MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 expressions (P<0.01), and downregulated Bcl-2, PCNA, and Cyclin D1 expressions (P<0.01). XMU-MP-1 inhibited the intervention effects of RS extracts (P<0.01).@*CONCLUSION@#RS extracts could inhibit proliferation and promote apoptosis and autophagy in thyroid tissues through MST1/Hippo pathway for treating hyperthyroidism.

Influência da via hippo em carcinomas de células escamosas de língua oral / Influence of the hippo pathway on oral tongue squamous cell carcinomas

O carcinoma de células escamosas de língua oral (CCELO) apresenta altas taxas de morbidade e mortalidade. Apesar dos progressos alcançados nesta área, os pesquisadores continuam em busca de biomarcadores moleculares que tenham valor preditivo no prognóstico dos pacientes e que possibilitem o desenvolvimento de novas estratégias terapêuticas. Neste contexto, várias pesquisas têm destacado o papel da via Hippo com esta finalidade. Portanto, esta pesquisa teve como objetivo avaliar se as proteínas relacionadas à Via Hippo, LATS2 e YAP1, exercem alguma influência sobre o comportamento biológico dos CCELOs. A amostra foi constituída por 26 casos de CCELO e 8 casos de mucosa oral normal como controle. Para avaliar a morfologia dos CCELOs foram utilizadas as gradações propostas pela OMS (2005) e por Almangush et al. (2014). O perfil imunoistoquímico de LATS2 e YAP1 foi avaliado por escores (0-3), com base na sua imunoexpressão em localização intracelular (núcleo e/ou citoplasma) e distribuição epitelial. Para a análise entre os parâmetros estudados foram realizados os testes estatísticos Qui-quadrado de Pearson e Exato de Fisher. A análise de sobrevida foi realizada através do método de Kaplan Meier e do teste log-rank. Para todas as avaliações foram considerados valores significativos com p<0,05. Foi observada alta expressão da LATS2 tanto em mucosa oral normal (100%) quanto na maioria dos CCELOs (73,1%), sem diferença estatística significativa (p=0,160). Foi possível evidenciar o aumento da imunoexpressão da YAP nos casos de CCELO em comparação à mucosa oral normal (p<0,001). Verificou-se ainda que a baixa expressão da LATS2 foi associada com menores taxas de sobrevida livre da doença (p=0,039). Além disso, constatou-se que a elevada expressão da YAP foi associada à classificação de alto risco do modelo BD (p=0,034), sugerindo que a imunoexpressão desta proteína pode estar associada a TEM e invasão celular em CCELO. A elevada expressão de ambas as proteínas, na maioria dos CCELOs, sugere que outras vias de sinalização, além da regulação através da LATS2, podem estar induzindo a expressão nuclear de YAP nestes tumores. Portanto, conclui-se que a via Hippo pode influenciar o comportamento biológico dos CCELOs (AU).

Oral tongue squamous cell carcinoma (OTSCC) has high morbidity and mortality rates. Despite the progress made in this area, researchers continue to search for molecular biomarkers that have predictive value in the prognosis of patients and allow the development of new therapeutic strategies. In this context, several studies have highlighted the role of the Hippo pathway for this purpose. Therefore, this research aimed to evaluate whether the proteins related to the Hippo pathway, LATS2 and YAP1, have some influence on the OTSCC biological behavior. The sample consisted of 26 OTSCC cases and 8 normal oral mucosa cases as control. For the morphological assessment of OTSCC, the gradations proposed by the WHO (2005) and by Almangush et al. (2014) were performed. The immunohistochemical profile of LATS2 and YAP1 was evaluated by scores (0-3), based on their immunoexpression in intracellular location (nucleus and/or cytoplasm) and epithelial distribution. Pearson's Chi-square and Fisher's Exact statistical tests were performed for the analysis of the studied parameters. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. For all evaluations, values with p<0.05 were considered significant. High expression of LATS2 was observed both in normal oral mucosa (100%) and in most OTSCC (73,1%), with no statistically significant difference (p=0,160). It was possible to observe the increase in YAP immunoexpression in cases of OTSCC compared to the normal oral mucosa (p<0.001). It was also found that the LATS2 low expression was associated with lower rates of disease-free survival (p=0.039). Furthermore, YAP high expression was found associated with the BD model's high-risk classification (p=0.034), suggesting this protein immunoexpression may be associated with EMT and cell invasion in OTSCC. The high expression of both proteins in most OTSCC suggests that other signaling pathways, in addition to regulating through LATS2, may be inducing the nuclear YAP expression in these tumors. Therefore, it is concluded that the Hippo pathway can influence the OTSCC biological behavior (AU).

Internal relationship between Hippo pathway and pulmonary hypertension / 中国胸心血管外科临床杂志

@#Pulmonary hypertension is a kind of progressive pulmonary vascular diseases in which there is excessive vasoconstriction and abnormal pulmonary vascular remodeling, and then a gradual increase in pulmonary arterial pressure, and it eventually leads to right ventricular failure and even death. The pathogenesis of pulmonary hypertension is still uncertain, but some studies suggest that Hippo pathway or some components of the Hippo pathway may be involved in the progress of pulmonary hypertension. In this review, we describe the mechanism of the Hippo pathway or some components of the Hippo pathway in the progress of pulmonary hypertension.

Effects of Hippo signaling pathway on lung injury repair by mesenchymal stem cells in acute respiratory distress syndrome / 中华危重病急救医学

OBJECTIVE@#To investigate the effects of Hippo signaling pathway on lung injury repair of mesenchymal stem cells (MSC) in acute respiratory distress syndrome (ARDS) and its mechanism.@*METHODS@#Mouse bone marrow-derived MSC (mMSCs) cell lines with low expression of large tumor suppressor 2 (LATS2) were constructed by lentiviral vector transfection. Male C57BL/6 mice aging 6-8 weeks old were divided into four groups according to random number table (n = 36). The ARDS animal model (ARDS group) was reproduced by intratracheally injection of 2 g/L lipopolysaccharide (LPS) 50 μL, the normal saline (NS) control group was injected with an equal volume of NS. After 4 hours of model reproduction, 5×104 mMSCs transfected with blank lentivirus vector (MSC-shcontrol group) or shLATS2 lentivirus vector (MSC-shLATS2 group) were transplanted intratracheally, while NS control group and ARDS group were injected with equal volume of phosphate buffered saline (PBS). Mice were sacrificed at 3, 7, and 14 days after modeling, and lung tissue and bronchoalveolar lavage fluid (BALF) were harvested. Near-infrared fluorescence imaging, immunofluorescence staining and Western Blot were used to track mMSCs in lung tissue. Retension and proportion of mMSC differentiation into type II alveolar epithelial cells (AEC II) were evaluated. Lung tissue wet weight/body weight ratio (LWW/BW) and total protein (TP) and albumin (ALB) in BALF were determined to reflect pulmonary edema. The expression of Occludin protein in lung epithelium was tested by Western Blot to reflect permeability of epithelium. The levels of interleukins (IL-1β, IL-6, IL-10) in BALF were assessed by enzyme-linked immunosorbent assay (ELISA) to reflect lung inflammation. Hematoxylin-eosin (HE) staining and modified Masson staining were carried out, and the scores were assessed to reflect lung injury and evaluate pulmonary fibrosis.@*RESULTS@#The signal intensity of isolated lung fluorescence images at 3 days in the MSC-shLATS2 group was significantly higher than that in the MSC-shcontrol group (fluorescence intensity: 0.039±0.005 vs. 0.017±0.002, P < 0.05), the number of green fluorescent protein (GFP)-positive cells in lung tissue was also significantly higher than that in the MSC-shcontrol group (cells/HP: 29.65±6.98 vs. 17.50±4.58, P < 0.05), but they all decreased with time; and the proportion of mMSCs differentiated into AEC II was significantly increased [(64.12±15.29)% vs. (19.64±3.71)%, P < 0.05]. Compared with the NS control group, the levels of surface active protein C (SPC) and Occludin protein in the ARDS group were significantly decreased, LWW/BW ratio and TP, ALB and inflammatory factors levels in BALF were significantly increased; extensive alveolar and interstitial edema, hemorrhage and diffuse inflammatory cell infiltration were found in lung tissue, and the lung injury score was significantly increased; collagen fibers were deposited in alveolar septum and alveolar cavity, and pulmonary fibrosis score was also increased significantly. Compared with the ARDS group, the expression levels of SPC and Occludin at 14 days in the MSC-shcontrol group and the MSC-shLATS2 group were significantly increased (SPC/β-actin: 0.51±0.12, 0.68±0.10 vs. 0.27±0.08, Occludin/β-actin: 0.49±0.19, 0.79±0.11 vs. 0.25±0.08, all P < 0.05), TP, ALB, IL-1β, IL-6 levels in BALF at 3 days were significantly decreased [TP (g/L): 8.08±1.72, 5.12±0.87 vs. 12.55±2.09; ALB (g/L): 0.71±0.21, 0.44±0.18 vs. 1.18±0.29, IL-1β (ng/L): 99.26±14.32, 60.11±8.58 vs. 161.86±25.17, IL-6 (ng/L): 145.54±13.29, 101.74±11.55 vs. 258.79±27.88, all P < 0.05], and IL-10 was significantly increased (ng/L: 190.83±22.61, 316.65±37.88, both P < 0.05). Furthermore, all the above parameters in the MSC-shLATS2 group were significantly improved as compared with those in the MSC-shcontrol group (all P < 0.05). LWW/BW ratio in the MSC-shLATS2 group was significantly lower than that in the ARDS group and the MSC-shcontrol group (mg/g: 9.85±1.51 vs. 16.78±1.92, 14.88±1.74, both P < 0.05).@*CONCLUSIONS@#Inhibiting Hippo signaling pathway by low expression of LATS2 could promote the retention of mMSCs in lung tissue and differentiation into AEC II cells of ARDS mice, improve pulmonary edema and alveolar epithelial permeability, regulate pulmonary inflammatory response, and alleviate pathological damage and fibrosis of lung tissue.

Role of cytoplasmic lncRNAs in regulating cancer signaling pathways / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Cancer remains a serious healthcare problem despite significant improvements in early detection and treatment approaches in the past few decades. Novel biomarkers for diagnosis and therapeutic strategies are urgently needed. In recent years, long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in tumors and show crosstalk with key cancer-related signaling pathways. In this review, we summarized the current progress of research on cytoplasmic lncRNAs and their roles in regulating cancer signaling and tumor progression, further characterization of which may lead to effective approaches for cancer prevention and therapy.