Livin is protective in UVB-induced skin photodamage by regulating keratinocyte activation and inflammatory responses.

UVB radiation can lead to skin photodamage, which might arise from keratinocyte (KC) activation. Nuclear factor kappa B (NF-κB) assumes an essential function in the context of UVB-triggered skin photodamage. Initiating the NF-κB cascade leads to the release of inflammatory factors from KCs. Livin can modulate both KC activation and function, yet it remains uncertain whether and how Livin regulates KC activation induced by UVB. To explore the involvement of Livin in UVB-triggered skin photodamage and its impact on skin damage through NF-κB activation. Immunofluorescence staining was used to analyse the expression of Livin in individuals with skin photodamage and in mice treated with UVB radiation. KC-specific Livin knockout (LivinΔKC ) mice and HaCaT cells with Livin knockdown were employed to examine the function of Livin in regulating KC activation induced by UVB radiation. Additionally, the impact of Livin on the NF-κB cascade during KC activation was confirmed via western blot analysis. In patients with skin photodamage, UVB-treated mice and HaCaT cells, Livin expression was reduced in KCs. LivinΔKC mice displayed heightened sensitivity to UVB radiation, resulting in more pronounced skin damage and inflammatory responses compared to the control Livinfl/fl mice. Following UVB exposure, both LivinΔKC mice and Livin-knockdown HaCaT cells released elevated levels of cytokines compared to their respective controls. Moreover, the UVB-induced activation of NF-κB in HaCaT cells was significantly enhanced following Livin knockdown. Our findings propose that Livin within KCs could contribute to reducing UVB-induced skin photodamage by regulating the NF-κB pathway.

Livin expression promotes keratinocyte release of inflammatory mediators in psoriasis.

BACKGROUND: Psoriasis is a prevalent, long-term skin condition characterized by inflammation. Keratinocytes (KCs) are important effector cells that release inflammatory factors and chemokines to promote the inflammatory cascade in psoriasis. However, the mechanisms underlying the activation of KCs in psoriasis remain unclear. Livin suppresses apoptotic proteins and directly affects the growth and spread of cancer cells. Livin expression reportedly increases significantly in lesions of patients with psoriasis; however, its specific role in KC activation remains unknown. This study aimed to examine the impact of Livin on KC activation and the subsequent release of inflammatory mediators. METHODS: Immunofluorescence staining, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and western blotting were used to assess Livin expression in patients with psoriasis, an imiquimod (IMQ)-induced psoriasis-like mouse model, and M5-treated HaCaT cells. To investigate the role of Livin in KCs, we performed RNA sequencing and proteomic analysis of Livin-knockdown (knockdown-HaCaT) and negative control (NC-HaCaT) cells. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for enrichment analyses. Moreover, the effect of Livin expression on the release of inflammatory mediators in KCs was verified using ELISA. RESULTS: Livin expression was higher in KCs of patients with psoriasis than in those healthy controls. Livin expression in HaCaT cells treated with M5 increased significantly over time. Livin expression was higher in the skin lesions of the IMQ mouse model than in the control group. Proteomic analysis and RNA sequencing used to investigate the function of Livin in HaCaT cells revealed its potential role in mediating KC activation and inflammatory mediator release, which affected the pathology of psoriasis. CONCLUSIONS: Livin expression played an effect on KCs activation, which induced release of inflammatory mediators and up-regulation of keratin. This study provides a new effector molecule for the mechanism of inflammatory response in psoriasis.

RNA-seq reveals novel mechanistic targets of Livin in bladder cancer.

BACKGROUND: Bladder cancer is a very common malignancy with a high recurrence rate. The survival of patients with muscle-invasive bladder cancer is poor, and new therapies are needed. Livin has been reported to be upregulated in bladder cancer and influence the proliferation of cancer cells. MATERIALS AND METHODS: The Livin gene in human bladder cancer cell line T24 was knocked out, and the differentially expressed genes were identified by RNA-seq and qPCR. RESULTS: Livin knockdown affects gene expression and has strong negative effects on some cancer-promoting pathways. Furthermore, combined with bladder cancer clinical sample data downloaded from TCGA and GEO, 2 co-up-regulated genes and 58 co-down-regulated genes were identified and validated, which were associated with cancer proliferation and invasion. CONCLUSION: All these results suggest that Livin plays an important role in bladder cancer and could be a potential anticancer target in clinical therapy.

The clinicopathological and prognostic significances of IGF-1R and Livin expression in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. However, limited effective biomarkers are associated with the tumorigenesis and prognosis of CRC. METHODS: The present study identified potential signatures from The Cancer Genome Atlas (TCGA) database and further validated the identified biomarkers in CRC tissues by immunohistochemistry (IHC). RESULTS: The expression of insulin-like growth factor 1 receptor (IGF-1R) and Livin gene was significantly upregulated in CRC samples compared to the adjacent normal samples in the TCGA dataset. IHC indicated that IGF-1R and Livin protein levels are increased in CRC and adenoma tissues compared to normal tissues. Notably, the IGF-1R protein levels differed significantly between adenoma and CRC. The elevated IGF-1R and Livin expression was associated with CRC clinicopathological features, including age, gender, histological subtype, individual cancer stages, nodal metastasis, and TP53-mutant in TCGA. Additionally, the IGF-1R promoter methylation level was closely related to CRC. Consistent with the TCGA study, IHC indicated that overexpressed IGF-1R and Livin proteins were independent risk factors for stage and metastasis. A marked correlation was established between IGF-1R and Livin expression in CRC, while the survival map showed no significant correlation with CRC. Kaplan-Meier survival curves showed that CRC patients with high IGF-1R or Livin expression had a prolonged overall disease-free survival than those with low expression in TCGA. CONCLUSION: IGF-1R and Livin are associated with CRC tumorigenesis and might be valuable for novel biomarker identification and targeted therapeutic strategy development.

Methylation-mediated miR-214 regulates proliferation and drug sensitivity of renal cell carcinoma cells through targeting LIVIN.

LIVIN, a member of the inhibitor of apoptosis proteins (IAPs), is reported playing important roles in the development and progression of multiple human cancers. However, its underlined mechanisms in human renal cell carcinoma (RCC) are still needed to be clarified. In the present study, we reported that inhibition of miR-214 promoted the expression of LIVIN, then facilitated RCC cells growth and reduced the sensitivity of RCC cells to chemotherapeutic drugs. In constant, overexpression of miR-214 had contradictory effects. Further investigation showed that miR-214 was down-regulated in RCC because of abnormal methylation. In addition, DNA methyltransferase DNMT1, miR-214 and LIVIN are directly correlated in RCC patients. In conclusion, these results suggest that abnormal miR-214 methylation negatively regulates LIVIN, which may promote RCC cells growth and reduced the sensitivity of RCC cells to chemotherapeutic drugs.

Oncostatin M upregulates Livin to promote keratinocyte proliferation and survival via ERK and STAT3 signalling pathways.

NEW FINDINGS: What is the central question of this study? What controls the proliferation and apoptosis in the pathogenesis of psoriasis? What is the main finding and its importance? The pathogenesis psoriasis involves abnormal homeostasis of keratinocytes, with hyperproliferation and decreasing apoptosis. An inhibitor of apoptosis protein family molecule, Livin, is highly expressed in psoriasis vulgaris lesional skin tissue. Expression of Livin was upregulated at transcription and protein levels after stimulation with oncostatin M (OSM). OSM promoted the survival of HaCaT cells in oxidative stress conditions. Expression of Livin and proliferation of HaCaT cells stimulated by OSM was regulated through ERK and STAT3 signalling pathways. This study might provide new insights into targeted therapy for psoriasis. ABSTRACT: Psoriasis is an immune-mediated chronic inflammatory disease. Abnormal homeostasis of keratinocytes, with hyperproliferation and decreasing apoptosis, is involved in the pathogenesis of psoriasis. Here, we report that an inhibitor of apoptosis protein family molecule, Livin, is highly expressed in psoriasis vulgaris lesional skin tissue at transcription and protein levels. Importantly, the expression level of Livin is related to the severity of psoriasis. The aim of the study was to investigate the regulation and functions of Livin in keratinocytes stimulated by the pro-inflammatory cytokine oncostatin M (OSM). The expression of Livin in HaCaT cells at mRNA and protein levels was measured by real-time PCR and Western blotting after OSM stimulation. The cell proliferation was measured by a 5-ethynyl-2'-deoxyuridine incorporation assay. Cell death was induced by the exogenous hydrogen peroxide (H2 O2 ) stress model, detected by 7-amino-actinomycin D staining and analysed by flow cytometry. Livin was overexpressed by a lentiviral transduction system to validate the roles of OSM and Livin in HaCaT cells. Specific inhibitors of ERK (U0126) and STAT3 (cryptotanshinone) were applied to investigate the signalling pathways involved in the regulation of Livin expression by OSM. The expression of Livin was upregulated after stimulation with OSM. OSM promoted the proliferation and survival of HaCaT cells. The expression of Livin and the proliferation of HaCaT cells induced by OSM were regulated through the ERK and STAT3 signalling pathways. We conclude that OSM promotes HaCaT cell proliferation and survival in conditions of oxidative stress.

Expression of inhibitors of apoptosis proteins in salivary gland adenoid cystic carcinoma: XIAP is an independent marker of impaired cause-specific survival.

OBJECTIVES: Inhibitors of apoptosis proteins are crucial to carcinogenesis since their expression results in evasion of apoptosis. Overexpression of inhibitors of apoptosis has repeatedly been associated with resistance to treatment and poor prognosis in various cancers. The role of inhibitors of apoptosis in adenoid cystic carcinoma of the salivary gland is still unclear. The aim of this study was to investigate the expression of inhibitors of apoptosis and their potential prognostic value in adenoid cystic carcinoma. DESIGN, SETTING AND PARTICIPANTS: Forty-nine patients, diagnosed with adenoid cystic carcinoma of the salivary gland between 1996 and 2016, were retrospectively included in this study. The expression of cIAP1, cIAP2, XIAP, Birc6, Livin and Survivin was assessed using immunohistochemistry, and their association of survival and prognosis was evaluated during a median follow-up of 6.4 years. MAIN OUTCOME MEASURE: Cause-specific survival and recurrence-free survival rates. RESULTS: XIAP, cIAP2, Livin and nuclear Survivin showed high expression levels in adenoid cystic carcinoma in most patients. There was no significant association of cIAP1, cIAP2, Livin, Birc6 and Survivin with outcome. However, high XIAP expression was associated with worse cause-specific survival and worse response to radiotherapy and proved to be an independent marker in multivariable analysis. CONCLUSION: Our data indicate that high expression of XIAP may be used as a prognosticator for poor survival and poor response to radiotherapy in adenoid cystic carcinoma patients.

Expression of antiapoptotic proteins livin and survivin in pediatric AML patients, as prognostic markers.

OBJECTIVE: Survivin and livin are highly expressed in various malignancies and their expression levels may be related to unfavorable prognosis. The aim was to investigate the relationships of these two markers with some prognostic factors and with survival of the children with acute myeloid leukemia (AML). METHODS: Livin and survivin expression was investigated quantitatively by immunohistochemistry staining technique in 43 primary formalin-fixed, paraffin-embedded bone marrow blocks in pediatric age group (<18 years). RESULTS: Both survivin and livin were expressed in 81.4% of AML patients. Livin expression showed significant positive association with high level of primary WBC (p = .002). Survivin expression showed significant positive correlations with risk of relapse (p ≤ .001) and high level of primary WBC (p = .003). The relationship of overall survival (OS) of the patients with livin and survivin expression, were investigated separately in disease subtypes. Significant association was observed between survivin expression and shorter OS regardless of subtypes including acute promyelocytic (APL) (p = .01) and nonacute promyelocytic leukemia (non-APL) (p = .008). Also, significant association of livin expression with shorter OS was detected, but only in APL subgroup (p = .046). Nevertheless, in Cox regression model after adjusting for disease subtypes, stage and cytogenetics; survivin and livin showed no significant association with OS (p > .05). CONCLUSION: Livin and survivin showed significant associations with some poor prognostic factors of AML. Although survivin in both subtypes and livin in non APL subtype, showed a significant relationship with shorter OS, none of them was determined as independent prognostic factors. Further studies with larger sample size are suggested.

Single-chain antibody-delivered Livin siRNA inhibits human malignant melanoma growth in vitro and in vivo.

Although gene therapy has brought new insights into the treatment of malignant melanoma, targeting delivery of nucleic acid which targets critical oncogene/anti-oncogene in vivo is still a bottleneck in the therapeutic application. Our previous in vitro studies have found that the oncogene Livin could serve as a potential molecular target by small interfering RNA for gene therapy of malignant melanoma. However, how to transport Livin small interfering RNA into malignant melanoma cells specifically and efficiently in vivo needs further investigation. Cumulative evidence has suggested that single-chain antibody-mediated small interfering RNA targeted delivery is an effective way to silence specific genes in human cancer cells. Indeed, this study designed a protamine-single-chain antibody fusion protein, anti-MM scFv-tP, to deliver Livin small interfering RNA into LiBr cells. Further experiments confirmed the induction of cell apoptosis and suppression of cell proliferation by anti-MM scFv-tP in LiBr cells, along with efficient silence of Livin gene both in vitro and in vivo. Altogether, our findings provide a feasible approach to transport Livin small interfering RNA to malignant melanoma cells which would be a new therapeutic strategy for combating malignant melanoma.

LncRNA CCAT1 inhibits cell apoptosis of renal cell carcinoma through up-regulation of Livin protein.

This study was to investigate the involvement of long non-coding RNA (lncRNA) colon cancer-associated transcript-1 (CCAT1) in renal cell carcinoma (RCC) and to further uncover its underlying mechanism. In this study, the expression of CCAT1 and Livin of RCC tissues or cells was determined using qRT-PCR (quantitative real-time PCR) and western blot, respectively. RNA pulldown and RIP (RNA-Binding Protein Immunoprecipitation) assays were performed to examine the sequence interaction between CCAT1 and Livin. The viability and apoptosis of RCC cells was assessed by MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and TUNEL (TdT-mediated dUTP nick end labeling) assays, respectively. Mice of tumor animal models were established to observe the effect of CCAT1 on RCC tumor growth. The relative expression of CCAT1 in RCC tissues and cell lines was obviously higher than that of the control. CCAT1 knockdown could reduce cell viability and increase the apoptosis of RCC cells in vitro. Furthermore, Livin was significantly inhibited by CCAT1 silencing; RNA pulldown and RIP assays showed that CCAT1 was physically associated with Livin protein. Moreover, Livin overexpression not only significantly inhibited RCC cell apoptosis and increased cell viability, but completely reversed the si-CCAT1-mediated repression of cell viability. More importantly, CCAT1 silencing could inhibit the growth of RCC in vivo that was accompanied by the reduction of Livin in RCC tissues. CCAT1 inhibits RCC cell apoptosis and increases cell viability through up-regulation of Livin.

CYLD downregulates Livin and synergistically improves gemcitabine chemosensitivity and decreases migratory/invasive potential in bladder cancer: the effect is autophagy-associated.

Although GC (gemcitabine and cisplatin) chemotherapy remains an effective method for treating bladder cancer (BCa), chemoresistance is a major obstacle in chemotherapy. In this study, we determined whether gemcitabine resistance correlates with migratory/invasive potential in BCa and whether this relationship is regulated by the cylindromatosis (CYLD)-Livin module. First, we independently investigated the correlation of CYLD/Livin and gemcitabine resistance with the potential for tumor migration and invasiveness. Second, we found that co-transfected CYLD and Livin dramatically improved sensitivity to gemcitabine chemotherapy and decreased migration/invasion potential. Next, we determined that CYLD may regulate Livin by the NF-κB-dependent pathway. We also found that CYLD overexpression and Livin knockdown might improve gemcitabine chemosensitivity by decreasing autophagy and increasing apoptosis in BCa cells. Finally, the effects of CYLD-Livin on tumor growth in vivo were evaluated. Our study demonstrates that CYLD-Livin might represent a potential therapeutic for chemoresistant BCa.

Silencing Livin induces apoptotic and autophagic cell death, increasing chemotherapeutic sensitivity to cisplatin of renal carcinoma cells.

Renal cell carcinoma (RCC) accounts for 3 % of all adult malignancies and is the most lethal urological cancer. Livin is a member of the inhibitor of apoptosis protein (IAP) family, which is associated with tumor resistance to radiotherapy and chemotherapy. Clinical data also showed that patients with high tumor grades and stages have higher expression levels of Livin in RCC cells. Autophagy is a survival mechanism activated in response to nutrient deprivation. A possible role of Livin in the autophagy of RCC cells has not been investigated; therefore, this pioneer study was carried out. Livin was silenced in RCC cells (slow virus infection [SVI]-shLivin cells) by lentiviral transfection. Then, mRNA and protein expression levels in the transfected cells were assessed by quantitative fluorescence PCR and Western blotting, respectively. In addition, acridine orange staining and electron microscopy were used to assess autophagy in SVI-shLivin cells. The cisplatin IC50 values for RCC cells were measured by the CCK8 assay. Potent antitumor activities were observed in xenograft mouse models generated with Livin-silenced RCC cells in terms of delayed tumor onset and suppressed tumor growth. These results suggested that Livin silencing could increase the chemotherapeutic sensitivity of RCC cells to cisplatin and induce autophagic cell death. A possible mechanism of Bcl-2 and Akt pathway involvement was discussed specifically in this study. Overall, Livin silencing induces apoptotic and autophagic cell death and increases chemotherapeutic sensitivity of RCC cells to cisplatin.

Construction of a Hep-2 cell line stably transfected with Livin shRNA.

OBJECTIVE: The aim of this study was to construct a eukaryotic expression plasmid with a short hairpin RNA (shRNA) targeting Livin in order to obtain a stably transfected Hep-2 cell line with a reduced expression of Livin. METHODS: The shRNA targeting Livin mRNA was designed, and a shRNA plasmid and a negative control plasmid were constructed. After amplification in E. coli, restriction endonuclease digestion and sequence confirmation, the plasmids were transfected into Hep-2 cells using Lipofectamine 2000. The stably transfected cell line was screened using G418, and inhibition of Livin mRNA and protein levels were detected using real-time PCR and western blotting, respectively. RESULTS: pGenesil-Livin-shRNA eukaryotic expression plasmid was successfully constructed and identified by sequencing. Green fluorescent protein (GFP) expression was observed in Hep-2 cells transfected with shRNA plasmids by fluorescence microscopy. The expression levels of Livin mRNA and protein decreased significantly in Hep-2 cells transfected with the shRNA recombinant plasmid. The mRNA level was reduced by 47.17 %, and the protein level was reduced by 34.25 %. CONCLUSION: The shRNA eukaryotic expression plasmid targeting Livin was successfully constructed, which could significantly inhibit the expression of Livin in laryngeal cancer Hep-2 cells. This provides a basis for future research on the function of Livin in Hep-2 cells, and gene therapy for laryngeal cancer.

[Expressions of Livin and PTEN in Cancerous Tissues of Ovary Endometriosis].

OBJECTIVES: To investigate the expressions of Livin and phosphate and tension homology deleted on chromsome ten (PTEN) protein in the cancerous tissues of ovary endometriosis. METHODS: Immunohistochemistry EliVision was used to examine the expressions of Livin and PETN protein in 19 samples of ovary endometriosis cancerous tissues, 30 samples of ovary endometriosis tissues and 30 samples of ovarian benign tumor tissues. RESULTS: The positive expression rate of Livin in ovary endometriosis cancerous tissues (68%) was obviously higher than that in ovary endometriosis tissues (36%) and benign tumor tissues (13%)( P<0.05). The positive expression rate of PTEN in ovary endometriosis cancerous tissues (16%) was obviously lower than that in ovary endometriosis tissues (65%) and benign tumor tissues (80%)( P<0.01). There was no correlations between positive expressions of Livin and age, clinical stage, grading, histological type and lymphatic metastasis of ovary endometriosis cancer ( P>0.05), the same result was also found for PTEN. Livin and PTEN expression presented an obviously negative correlation in ovary endometriosis cancer ( r=-0.559, P=0.001). CONCLUSIONS: Up-regulation of Livin expression and down-regulation of PTEN may be involved in the occurrence and development of ovary endometriosis cancerization.

In vitro antitumor immune response induced by dendritic cells transduced with human livin α recombinant adenovirus.

Transduction with recombinant, replication-defective adenoviral (rAd) vectors encoding a transgene is an efficient method for gene transfer into human dendritic cells (DCs). Livin is a good candidate for cancer immunotherapy since it is overexpressed in most common human cancers, poorly expressed in most normal adult tissues. Two splicing variants of livin, designated livin α and livin ß, have been identified. In this study, we used human livin α recombinant adenovirus (rAd-hlivin α) to transduced DCs. We found that DCs transduced with rAd-hlivin α (rAd-hlivin α DCs) could effectively induce human livin α specific cytotoxic T lymphocytes (CTL) in vitro against various tumor cell lines.

Livin is associated with the invasive and oncogenic phenotypes of human hepatocellular carcinoma cells.

AIM: Livin, a member of the inhibitors of apoptosis proteins, is expressed in variable cancers, and its expression is considered a poor prognostic marker. The aims of this study were to observe the effect of Livin on the behaviors of hepatocellular carcinoma (HCC) cells and to evaluate its expression in HCC tissues and its relation to prognosis. METHODS: The biological effects of Livin on tumor cell behavior were investigated using siRNA in HepG2 and Chang cells. Migration, invasion and proliferation assays were performed. Flow cytometric analyses and western blotting were used to evaluate the impact of Livin on apoptosis and the cell cycle. In addition, western blotting and immunohistochemistry were used to investigate Livin expression in HCC tissues. RESULTS: Livin knockdown suppressed tumor cell migration, invasion and proliferation in HCC cells, and increased the proportion of apoptotic cells as compared with scrambled siRNA-transfected HCC cells. Furthermore, Livin knockdown resulted in the activation of caspases and increased apoptosis. In addition, Livin knockdown modulated cell cycle regulatory protein levels such as decrease of cyclins and cyclin-dependent kinase (CDK) level, and increase of CDK inhibitor (CDKI) level in HCC cells. The Livin protein level was significantly elevated in HCC tissues as compared with normal hepatic tissues. However, Livin expression was not found to be associated with clinicopathological parameters, which included patient survival. CONCLUSION: These results suggest that Livin is associated with invasive and oncogenic phenotypes of human HCC cells.

Activation of nuclear factor κB pathway and downstream targets survivin and livin by SHARPIN contributes to the progression and metastasis of prostate cancer.

BACKGROUND: Nuclear factor κB (NFκB) signaling is strongly associated with tumor progression, and studies have shown that SHANK-associated RH domain interacting protein (SHARPIN) is crucial for NFκB pathway activation. However, the expression and functions of SHARPIN in prostate cancer (PCa) have not yet been defined. METHODS: The expression of SHARPIN in PCa cell lines and tissues was evaluated with western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. After SHARPIN was silenced in the PCa cell lines, western blots were used to confirm that SHARPIN physically associated with components of the NFκB pathway and the downstream targets (survivin and livin). The functions of SHARPIN in cell proliferation, migration, and invasion in vitro were measured with 5-(3-carboxymethoxyphenyl)-2-(4,5-dimenthylthiazoly)-3-(4-sulfophenyl)tetrazolium, inner salt (MTS), Transwell, and invasion assays, respectively. Flow cytometry was employed to evaluate cell apoptosis. Furthermore, tumorigenesis in vivo was examined with tumorigenicity assays. RESULTS: SHARPIN expression was upregulated in PCa cell lines and tissues. The knockdown of SHARPIN or incubation with Bay 11-7082 (an NFκB inhibitor) led to dramatically decreased levels of phosphorylated IκBα and phosphorylated p65 in comparison with the control group. Downregulation of survivin and livin due to SHARPIN inhibition was attributable to transcriptional repression (P < .05). Decreases in cell viability, migration, invasion, and survival with a higher sensitivity to docetaxel in vitro and with repressed tumorigenesis in vivo were observed upon SHARPIN silencing, and this was consistent with the results from inhibition of the NFκB pathway and its downstream targets. CONCLUSION: The current study demonstrates that overexpression of SHARPIN promotes activation of the NFκB pathway and downstream targets survivin and livin, which potentially contributes to PCa development.

Livin, a novel marker in lymphoma type distinction.

Despite advances in immunohistochemical and molecular diagnostics, there are persistent difficulties in differentiating between several subtypes of non-Hodgkin lymphoma (NHL) and classic Hodgkin lymphoma (CHL). Considering high level of livin expression in hematologic malignancies, we aimed to examine the utility of livin expression ratio, as an ancillary biomarker, in distinguishing CHL from NHL in ambiguous cases. We evaluated livin expression in 38 CHL, 23 NHL, and 39 nonneoplastic lymph nodes in paraffin-embedded blocks. Tissue microarray-based semiquantitative immunoflourecent staining was applied for protein expression. Criterion standard of diagnosis was based on selection of only definite cases and not the cases suspected by hemathopathologists. A significant difference was found in the livin/GAPDH mean ratio (M.R) of expression between NHL and CHL cases. A receiver operating characteristic curve analysis confirmed 0.6370 to be the best diagnostic cut-off value for the livin/GAPDH expression M.R in diffuse large B-cell lymphoma (DLBCL) (area under the curve = 0.944); it yielded 92% sensitivity, 94% specificity, likelihood ratios positive 17.5, and likelihood ratios negative 0.07 for diagnosing DLBCL from CHL. Mean ratio of livin/Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression seems to be a valuable index in differentiating DLBCL from CHL. We suggested an optimal cut-off point for livin/GAPDH expression M.R with a high sensitivity and specificity. Thus, in diagnostically difficult cases of DLBCL and CHL, focus on livin as marker may provide useful corroborative information.

MicroRNAs Regulate Inhibitor of Apoptosis Proteins (IAPs) in Colorectal Cancer.

Colorectal cancer (CRC) is the second most common cause of cancer mortality, with approximately 1.9 million new cases and 0.9 million deaths globally in 2020. One of the potential ways to treat colorectal cancer may be through the use of molecular methods to induce cell apoptosis. Apoptosis is a natural cellular event that regulates the growth and proliferation of body cells and prevents cancer. In this pathway, several molecules are involved; one group promotes this process, and some molecules that are representative of inhibitors of apoptosis proteins (IAPs) inhibit apoptosis. The most important human IAPs include c-IAP1, c-IAP2, NAIP, Survivin, XIAP, Bruce, ILP-2, and Livin. Several studies have shown that the inhibition of IAPs may be useful in cancer treatment. MicroRNAs (miRNAs) may be effective in regulating the expression of various proteins, including those of the IAPs family; they are a large subgroup of non-coding RNAs that are evolutionarily conserved. Therefore, in this review, the miRNAs that may be used to target IAPs in colorectal cancer were discussed.

Dendritic cells infected with recombinant adenoviral vector encoding mouse fibroblast activation protein-α and human livin α exert an antitumor effect against Lewis lung carcinoma in mice.

BACKGROUND: Fibroblast activation protein-α (FAP) and livin α are considered as cancer-associated fibroblasts (CAFs) and tumor-specific targets, respectively, for immunogenic tumor vaccines. This study is designed to decipher the antitumor effect of double-gene modified dendritic cells (DCs) on Lewis lung carcinoma (LLC). METHODS: By encoding mouse FAP cDNA and human livin α (i.e., hlivin α) cDNA into recombinant adenoviral vector (rAd), rAd-FAP, rAd-hlivin α, and rAd-FAP/hlivin α were constructed, which were then transduced into mouse DCs. LLC-bearinig mice were immunized with the infected DCs (5 × 105 cells/mouse), followed by calculation of tumor volume and survival rate. The identification of CAFs from mouse LLC as well as the determination on expressions of FAP and livin α, was accomplished by western blot. Cytotoxic T lymphocyte assay was harnessed to assess the effect of the infected DCs on inducing splenic lymphocytes to lyse CAFs. RESULTS: DCs were successfully transduced with rAd-FAP/hlivin α in vitro. FAP was highly expressed in CAFs. CAFs were positive for α-SMA and negative for CD45 and CD31. Livin α level was upregulated in mouse LLC. Immunization with rAd-FAP/hlivin α-transduced DCs suppressed LLC volume and improved the survival of tumor-bearing mice. Immunization with rAd-FAP/hlivin α-transduced DCs enhanced the cytotoxic effect of splenic lymphocytes on LLC tumor-derived CAFs. CONCLUSION: Injection with rAd-FAP/hlivin α-transduced DCs promotes immune-enhanced tumor microenvironment by decreasing CAFs and suppresses tumor growth in LLC mouse models.