Long non-coding RNA TP73-AS1 predicts poor prognosis and regulates cell proliferation and migration in cervical cancer

IntroductionCervical cancer is one of the most common malignant tumors in women, which seriously affects women’s health, especially in developing countries. This study aims to investigate novel molecular markers for poor prognosis of cervical cancer to achieve correct guidance of clinical treatment, accurate assessment of prognosis, and provide a new basis for the choice of reasonable treatment options for cervical cancer patients.Material and methodsQRT-PCR was employed to investigate the expression of lncRNA TP73-AS1 in cervical cancer tissues and cell lines. COX multivariate analysis showed the relationship between TP73-AS1 expression and clinicopathological features of patients with cervical cancer. Colony formation and MTT assay detected the effect of TP73-AS1 on proliferation of cervical cancer cells. The effect of TP73-AS1 on migration and invasion of cervical cancer cells was determined by the wound-healing assay and transwell assay. Western blot was performed to assess the expression of EMT markers.ResultsThis study showed that lncRNA TP73-AS1 was up-regulated in cervical cancer tissues and cell lines (p < 0.001), and high expression of TP73-AS1 could be considered as an independent prognostic factor (p < 0.05). Moreover, lncRNA TP73-AS1 promotes cervical cancer cell migration and invasion, and knockdown of TP73-AS1 inhibits the growth of cervical cancer cells (p < 0.001).ConclusionsOur results indicated that lncRNA TP73-AS1 was up-regulated in cervical cancer tissues and cell lines, predicting poor prognosis of cervical cancer and regulating cell proliferation and migration.     

Low Expression of EphB2, EphB3, and EphB4 in Bladder Cancer: Novel Potential Indicators of Muscular Invasion

PurposeEph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles of EphB receptors (EphB2, B3, and B4) in urinary bladder cancer.Materials and MethodsTissue microarray-based immunohistochemical analysis was used to investigate the expression patterns of EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining the extent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was more than moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression in bladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration.ResultsEphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4, 82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumor grade (EphB2, p<0.001; EphB3, p=0.032; EphB4, p<0.001) and muscular invasion (EphB2, p=0.002; EphB3, p=0.009; EphB4, p<0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph node involvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumor cell invasion, proliferation, and migration in comparison with untransfected cancer cells.ConclusionLow expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.     

The expression of long non-coding RNA HOTAIR in advanced hepatocellular carcinoma and its prognostic correlation with sunitinib therapy

IntroductionThe study was designed to assess the expression of long non-coding RNA HOTAIR (lncRNA HOTAIR) in tissues and peripheral blood of patients with advanced hepatocellular carcinoma (HCC). In addition, we also investigated the prognostic correlation between the expression level of lncRNA HOTAIR in tumour tissues and peripheral blood of patients with advanced HCC and sunitinib monotherapy.Material and methodsA total of 60 patients with advanced HCC who received sunitinib monotherapy and another 60 healthy individuals who were examined at the physical examination centre during the same period were included in the study. Real-time quantitative PCR (RT-QPCR) was used to determine the relative expression of lncRNA HOTAIR in tumour tissue, adjacent tissue, and peripheral blood of HCC patients as well as peripheral blood of healthy controls. Moreover, the clinicopathological information, overall survival (OS), and progression-free survival (PFS) were collected, followed by correlation analysis with lncRNA HOTAIR expression.ResultsThe expression of lncRNA HOTAIR was significantly higher in tumour tissues compared to that in adjacent tissues (t = 9.03, p < 0.001). The expression of lncRNA HOTAIR in peripheral blood of HCC patients was higher than that in healthy controls (t = 8.04, p < 0.001). There was a correlation between the expression of lncRNA HOTAIR in tumour tissue and peripheral blood in HCC patients (r = 0.638, p < 0.001). Patients with low lncRNA HOTAIR expression in tumour tissues harboured significantly longer OS (13.4 vs. 9.5, p < 0.001) and PFS (8.4 vs. 6.2, p < 0.001) compared to those with high expression. Consistently, patients with low lncRNA HOTAIR expression in peripheral blood had significantly prolonged OS (12.8 vs. 9.1, p < 0.001) and PFS (8.9 vs. 6.4, p < 0.001) compared to those with high expression. Patients with low expression both in tumour tissue and peripheral blood had prolonged OS (14.3 vs. 8.8, p < 0.001) and PFS (10.6 vs. 6.0, p < 0.001) compared to the rest of the patients. Cox regression analysis indicated that the expression level of lncRNA HOTAIR in tumour tissue and peripheral blood was an independent predictive factor of OS and PFS in patients with advanced HCC treated by sunitinib.ConclusionsThe expression of lncRNA HOTAIR was up-regulated in tumour tissue and peripheral blood in patients with advanced HCC. In addition, the expression level of lncRNA HOTAIR was one of the indicators predicting the effectiveness of sunitinib therapy.     

High expression of long non-coding RNA ANRIL is associated with poor prognosis in hepatocellular carcinoma

Introduction: long non-coding RNA ANRIL (lncRNA ANRIL) has been demonstrated to play a crucial role in cancer progression. However, its effects in hepatocellular carcinoma (HCC) have not been explored. The aim of this study was to investigate the clinical significance of lncRNA NRIL in human HCC. Methods: In this study, we determined for the first time the expression of lncRNA ANRIL in human HCC by quantitative Real-time-PCR analysis. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence lncRNA ANRIL and to explore the effects of reduced lncRNA ANRIL expression on cell growth and metastasis. Results: lncRNA ANRIL expression in HCC tissues was significantly higher than in the adjacent non-tumor tissues (P < 0.05). The expression of lncRNA ANRIL was remarkably associated with the histologic grade and TNM stage of HCC patients (P < 0.05). In addition, HCC patients with higher lncRNA ANRIL expression had significantly poorer overall survival (P < 0.05). Multivariate analysis suggested that high lncRNA ANRIL expression was an independent predictor of poor prognosis (P < 0.05). Moreover, in vitro assays revealed that the decreased expression of lncRNA ANRIL could suppress the cell proliferation, migration and invasion HCC cells. Conclusions: Our results suggest that lncRNA ANRIL may serve as an efficient clinical biomarker and a therapeutic target for HCC patients.     

Low expression of long non-coding RNA LET inhibits carcinogenesis of cervical cancer

Introduction: Long non-coding RNAs (lncRNAs) have been demonstrated to play key roles in tumorgenesis, and the lncRNA LET is down-regulated in several cancers. However, little is known about the function of lncRNA LET in human cervical cancer. The aim of this study was to investigate the clinical significance of lncRNA LET expression in cervical cancer. Methods: We examined the expression of lncRNA LET in 94 cervical cancer tissues and matched adjacent non-tumor tissues using quantitative real-time PCR and analyzed its correlation with the clinicopathological features. Results: The results showed that lncRNA LET expression in cervical cancer tissues was significantly down-regulated compared with the adjacent non-tumor tissues (P < 0.05). Decreased lncRNA LET expression was significantly correlated with FIGO stage, lymph node metastasis, and depth of cervical invasion (P < 0.05), but not other clinical characteristics. Moreover, cervical cancer patients with lncRNA LET lower expression have shown significantly poorer overall survival than those with higher lncRNA LET expression (P < 0.05). Univariate and multivariate analyses suggested that lncRNA LET expression served as an independent predictor for overall survival. Conclusions: Our data provided the first evidence that lncRNA LET may represent a prognostic marker and a potential therapeutic target for cervical cancer.     

Surgical treatment of endometrial cancer in developing countries: reasons to consider systematic two-step surgical treatment

OBJECTIVE:The aim of this study was to determine the lymph node status in a large cohort of women with endometrial cancer from the public health system who were referred to an oncology reference center in Brazil to identify candidates for the omission of lymphadenectomy based on clinicopathological parameters.METHODS:We retrospectively analyzed a cohort of 310 women with endometrial cancer (255 endometrioid, 40 serous, and 15 clear cell tumors) treated between 2009 and 2014. We evaluated the histological type, grade (low vs. high), tumor size (cm), depth of myometrial invasion (≤50%, >50%) and lymphovascular space invasion to determine which factors were correlated with the presence of lymph node metastasis.RESULTS:The factors related to lymph node involvement were tumor size (p=0.03), myometrial invasion (p<0.01), tumor grade (p<0.01), and lymphovascular space invasion (p<0.01). The histological type was not associated with the nodal status (p=0.52). Only twelve of 176 patients (6.8%) had low-grade endometrioid carcinoma, tumor size ≤2 cm and <50% myometrial infiltration.CONCLUSIONS:The omission of lymphadenectomy based on the histological type, grade, tumor size and depth of myometrial invasion is not likely to have a large impact on the surgical treatment of endometrial cancer in our population because most patients present with large and advanced tumors. New strategies are proposed that prioritize hysterectomy performed in a general hospital as soon as possible after diagnosis, followed by an evaluation of the need for lymph node dissection at a reference center.     

miR-126 regulated breast cancer cell invasion by targeting ADAM9

Accumulating evidence has shown that microRNAs (miRNAs) deregulation is commonly observed in human malignancies and crucial to cancer metastasis. Herein, we demonstrated that miR-126 play a suppressor role in human breast cancer cells invasion through the direct repression of a disintegrin and metalloprotease 9 (ADAM9). MiR-126 expression was investigated in forty cases of breast cancer specimens by real-time PCR. Transwell assay was conducted to explore the effects of miR-126 on the invasion of human breast cancer cell lines. The impact of miR-126 overexpression on putative target ADAM9 was subsequently confirmed by Western blot analysis. Our results indicated that miR-126 expression was frequently down-regulated in breast cancer specimens compared with adjacent normal tissues (P<0.05). Overexpression of miR-126 significantly reduced (P<0.05) the protein levels of ADAM9, further suppressed (P<0.05) breast cancer cell invasion in vitro. Meanwhile, knockdown of ADAM9 by small interfering RNA (siRNA) also inhibited (P<0.05) breast cancer cell invasion. Thus, our study revealed that miR-126 may act as a tumor suppressor via inhibition of cell invasion by downregulating ADAM9 in breast cancer development.     

A preliminary evaluation of oxidative stress in patients with gastric cancer before chemotherapy

IntroductionDue to an imbalanced redox status, cancer cells generate intrinsically higher levels of reactive oxygen species (ROS) compared to normal cells. Targeting ROS is an important therapeutic strategy for cancer as exemplified by cancer drugs, which induce ROS-dependent synergistic cytotoxicity in gastric cancer cells. The present study was designed to assess the level of selected oxidative stress biomarkers in blood plasma derived from gastric cancer patients.Material and methodsThe study assessed the oxidative/nitrative biomarkers in blood plasma isolated from 51 gastric (adenocarcinoma) cancer patients, compared to a control group of 32 healthy volunteers. Oxidative stress was evaluated using a panel of biomarkers such as plasma protein thiol groups and 3-nitrotyrosine levels as well as indicators of plasma lipid peroxidation, i.e. lipid hydroperoxides (LOOH) and thiobarbituric acid-reactive substances (TBARS). Additionally, the total antioxidant capacity of blood plasma (non-enzymatic capacity of blood plasma, NEAC) was also estimated.ResultsOur results showed that patients with gastric cancer had significantly different levels of thiol groups (lower, p < 0.001) and 3-nitrotyrosine (higher, p < 0.0001), LOOH (higher, p < 0.05), TBARS (higher, p < 0.05), NEAC (lower, p < 0.0001), compared to the control group.ConclusionsThe present study indicates considerable oxidative/nitrative stress in gastric cancer patients. Our pilot study shows that not a single marker, but a biomarker panel, may be a more reliable representation of oxidative stress in patients with gastric cancer.     

Combined therapy with cisplatin and 5-AZA-2CdR modifies methylation and expression of DNA repair genes in oral squamous cell carcinoma

The methylation and expression of DNA repair system genes has been studied in several tumor types. These genes have been associated with resistance to chemotherapy treatments by epigenetic regulation. Studies have yet to show the effects of combined therapy using an epigenetic drug (5-aza-2CdR) and cisplatin (CDDP) on DNA repair genes in oral squamous cell carcinoma (OSCC). This study proposed to investigate the effects of CDDP in combination with 5-aza-2CdR on the methylation of MGMT and MLH1 genes in oral cancer cells. Oral squamous cell carcinoma cell lineages (SCC-9, SCC-15, and SCC-25) were submitted to 72 hours of treatment: 0.1 μM CDDP (or 4.44 μM SCC-9), 0.1 μM and 0.3 μM 5-aza-2CdR (or 1 μM and 3 μM SCC-9), and the drugs in combination. Cell viability was assessed by MTT, DNA methylation of MGMT and MLH1 genes by Methylation Sensitivity High-Resolution Melting (MS-HRM), and the relative expression of the genes by RT-qPCR. The results show that all treatments reduced cell viability; however, in SCC-15 and SCC-9 (IC₅₀ value), 5-aza-2CdR promotes cell sensitization to cytotoxic effect of cisplatin. The MGMT promoter region was 100% demethylated in the SCC-15 and SCC-25 cells but partially (50%) methylated in SCC-9 before drug treatment. Treatment with IC₅₀ CDDP value kept the methylation status and decreased MGMT expression in SCC-9; MGMT gene in SCC-15 and SCC-25 cells became downregulated after treatment with 5-aza-2CdR. MLH1 was demethylated, but the treatments with low-doses and combined drugs decreased the expression in SCC-9 and SCC-25; however high doses of 5-aza-2CdR and drug combination with IC₅₀ value CDDP increased expression of MLH1 in SCC-9. The data presented suggest that epigenetic drugs associated with chemotherapy have clinical translational potential as a therapy strategy to avoid or reverse cancer resistance, requiring further investigation.     

Modulatory Potential of LncRNA Zfas1 for Inflammation and Neuronal Apoptosis in Temporal Lobe Epilepsy

PurposeThis study aimed to elucidate whether lncRNA ZFAS1 is involved in neuronal apoptosis and inflammation in temporal lobe epilepsy (TLE).Materials and MethodsNinety-six TLE patients were recruited, and their peripheral venous blood was gathered to determine Zfas1 expression with polymerase chain reaction. Neurons were separated from hippocampal tissue of newborn SD rats, and si-Zfas1 or pcDNA3.1-Zfas1 was transfected into the neurons. Inflammatory cytokines released by neurons were determined, and neuronal activities were evaluated through MTT assay, colony formation assay, and flow cytometry.ResultsSerum levels of Zfas1 were higher in TLE patients than in healthy controls (p<0.05). Furthermore, Zfas1 expression in neurons was raised by pcDNA3.1-Zfas1 and declined after silencing of Zfas1 (p<0.05). Transfection of pcDNA-Zfas1 weakened the viability and proliferation of neurons and increased neuronal apoptosis (p<0.05). Meanwhile, pcDNA3.1-Zfas1 transfection promoted lipopolysaccharide-induced release of cytokines, including tumor necrosis factor-α, interleukin (IL)-1, IL-6, and intercellular adhesion molecule-1 (p<0.05), and boosted NF-κB activation by elevating the expression of NF-κB p65, pIκBα, and IKKβ in neurons (p<0.05).ConclusionOur results indicated that lncRNA ZFAS1 exacerbates epilepsy development by promoting neuronal apoptosis and inflammation, implying ZFAS1 as a promising treatment target for epilepsy.     

Up-regulation of long non-coding RNA Sox2ot promotes hepatocellular carcinoma cell metastasis and correlates with poor prognosis

Background: Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA Sox2ot is up-regulated in some tumors. However, the contributions of Sox2ot to hepatocellular carcinoma (HCC) remain largely unknown. Methods: In the present study, expression of lncRNA Sox2ot was evaluated by quantitative real-time PCR in tumor tissues and adjacent non-tumor tissues in 84 HCC patients. The association of lncRNA Sox2ot expression with clinicopathological features and the prognosis of HCC patients were also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox’s proportional hazards model. Small interfering RNA assay was used to explore the function of lncRNA Sox2ot on HCC cell migration and invasion. Results: lncRNA Sox2ot expression level was significantly higher in HCC tissues compared with adjacent non-tumor tissues (P<0.05). High expression of lncRNA Sox2ot was associated with histological grade, TNM stage, and vein invasion. The 5-year overall survival of high lncRNA Sox2ot expression group was significantly shorter than that of low lncRNA Sox2ot expression group (P<0.05). The multivariate Cox regression analysis indicated that lncRNA Sox2ot expression was an independent prognostic factor for overall survival. In addition, the metastasis ability of HCC cells was significantly decreased by knocking down lncRNA Sox2ot expression. Conclusions: The results suggested that lncRNA Sox2ot played crucial roles in promoting HCC cell migration and invasion, and might represent a novel prognostic biomarker for HCC.     

MicroRNA 144 inhibits cell migration and invasion and regulates inflammatory cytokine secretion through targeting toll like receptor 2 in non-small cell lung cancer

IntroductionMicroRNAs (miRNAs) are endogenous small noncoding RNA molecules involved in modulation of cancer progression. Here, we investigated the possible role of miR-144 in non-small cell lung cancer (NSCLC) development.Material and methodsThe expression of miR-144 and TLR2 in NSCLC tissue and cell lines was determined by quantitative real-time PCR (qPCR). The TargetScan database was used to predict potential target genes of miR-144. Luciferase assay was used to verify the interaction between TLR2 and miR-144. TLR2 protein expression was measured by western blot. The secretion of interleukin (IL)-1β, IL-6 and IL-8 in A549 cells was detected by an ELISA kit. Cell migration and invasion were evaluated by wound healing assay and transwell assay, respectively.ResultsOur results showed that miR-144 was downregulated in NSCLC tissue and cell lines when compared with the normal tissues and cell line (p < 0.05). The protein level of TLR2 in NSCLC tissue and cell lines was significantly higher than that in normal lung tissues. Dual luciferase reporter gene assay showed that miR-144 could bind to the 3ʹUTR of TLR2 specifically. Up-regulation of miR-144 significantly decreased the expression of TLR2. Up-regulation of miR-144 or down-regulation of TLR2 could decrease cell migration, invasion and secretion of IL-1β, IL-6 and IL-8 in A549 cells. Moreover, overexpression of TLR2 rescued the inhibitory effects of miR-144 on migration, invasion and inflammatory factor secretion of A549 cells.ConclusionsmiR-144 could inhibit the migration, invasion and secretion of IL-1β, IL-6 and IL-8 through downregulation of TLR2 expression in A549 cells.     

Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective,Multi-Institutional Study

PurposeTo identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC).ResultsWith a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy.ConclusionA preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.     

FK506-binding protein 5 inhibits proliferation and stimulates apoptosis of glioma cells

Introduction

FK506-binding protein 5 (FKBP5) is reported to act as a scaffolding protein for Akt to promote the dephosphorylation of AKT Ser473 and suppress pancreatic cancer growth. However, other studies have shown that FKBP5 promotes tumor growth and chemoresistance through regulating NF-κB signaling in other cancers. In this study, we attempted to investigate the role and mechanism of action of FKBP5 in the regulation of proliferation and apoptosis of glioma cells.

Material and methods

The glioma U251 cell line was used as the model. Cell proliferation was detected by MTT assay. Cell apoptosis was detected by annexin-V staining. Protein expression was detected by Western blot analysis.

Results

FKBP5 overexpression inhibited the proliferation of U251 cells significantly (p < 0.05), and promoted the apoptosis of U251 cells significantly (p < 0.05). In addition, FKBP5 overexpression inhibited the phosphorylation of Akt at Ser743, decreased the level of Bcl-2, increased the level of Bax, and enhanced the cleavage of caspase-9 and caspase-3 (p < 0.05 compared to control). In contrast, FKBP5 knockdown enhanced the proliferation of U251 cells, increased the phosphorylation of Akt significantly (p < 0.05), increased the expression of Bcl-2 and decreased the expression of Bax, and decreased the cleavage of caspase-9 and caspase-3 significantly (p < 0.05).

Conclusions

FKBP5 plays the role of a tumor suppressor in glioma by inhibiting the activation of Akt and stimulating the intrinsic mitochondrial apoptotic pathway, and could be used as a new target for gene therapy of glioma.     

LINC00662 Promotes Oral Squamous Cell Carcinoma Cell Growth and Metastasis through miR-144-3p/EZH2 Axis

PurposeLong non-coding RNA (lncRNA) is identified as an important regulator involved in oral squamous cell carcinoma (OSCC) tumorigenesis. This study aimed to investigate the functional role and underlying mechanism of LINC00662 in OSCC.Materials and MethodsThe expression levels of LINC00662, miR-144-3p, and enhancer of zeste homolog 2 (EZH2) mRNA were quantified with quantitative real-time polymerase chain reaction in OSCC tissues and cell lines. Western blot analysis was used to assay the expression levels of E-cadherin, Vimentin, and EZH2. Cell proliferation, migration, and invasion were monitored by cell counting kit-8 and Transwell assays. Dual-luciferase reporter and RNA immunoprecipitation assays were employed to verify the regulatory relationship between LINC00662 and miR-144-3p.ResultsThe expression of LINC00662, positively associated with the increased TNM stage and lymph node metastasis of the patients, was up-regulated in OSCC tissues and cells. The overexpression of LINC00662 facilitated the proliferation, migration, and invasion of OSCC cells. MiR-144-3p could bind to LINC00662, and the promoting effect of LINC00662 overexpression was counteracted by miR-144-3p mimic. Moreover, EZH2 expression was negatively regulated by miR-144-3p and positively regulated by LINC00662. The silencing of EZH2 attenuated the promoting effects of overexpression of LINC00662 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition.ConclusionLINC00662, as an oncogenic lncRNA of OSCC, accelerates OSCC progression by repressing miR-144-3p expression and increasing EZH2 expression.     

Expression and clinical significances of Beclin1, LC3 and mTOR in colorectal cancer

Autophagy is related to cancer and other diseases, and compromised autophagy could promote chromosome instability associated with carcinogenesis and tumor progression. The role of autophagy in the growth and metastasis of colorectal cancer (CRC) remains poorly understood. Beclin1 mediates autophagic initiation, and LC3 is a specific marker for autophagy. Inactivation of mTOR caused by cellular hypoxia or energy deficiency induces autophagic activity. This study aims to examine the expression and clinical significance of these proteins in CRC. Immunohistochemistry results showed that the positive expression rates of Beclin1, LC3, and mTOR in cancer tissues were 90.50%, 87.19%, and 46.28%, respectively, which were higher than those in adjacent tissues (P < 0.05). Differentiation degree and lymph node metastasis were associated with LC3 overexpression (P < 0.05) but not with Beclin1 (P > 0.05). Lymph node metastasis was also related to mTOR. Spearman analysis results showed that LC3 expression was positively correlated with Beclin1 but negatively correlated with mTOR (r = 0.593 and -0.165, respectively; P < 0.01). Beclin1 expression was also not associated with mTOR (P > 0.05). Survival analysis further indicated that LC3, mTOR, and lymph node metastasis were independent prognostic factors in CRC. Real-time PCR results and Western blot indicated that Beclin1, LC3, and mTOR expression in CRC was significantly higher than that in adjacent tissues (P < 0.01). The aberrant protein expression may be associated with the development and progression of CRC. The LC3 and mTOR genes must be simultaneously detected to evaluate progression and prognosis of CRC.     

Polymeric immunoglobulin receptor (PIGR) exerts oncogenic functions via activating ribosome pathway in hepatocellular carcinoma

Objective: This report aimed to investigate the potential mechanism of polymeric immunoglobulin receptor (PIGR) in promoting cancer development in hepatocellular carcinoma (HCC).Methods: PIGR expression was investigated in Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) databases. Relationships between PIGR and HCC survival and clinico-pathological features were conducted in TCGA. RNAseq of PIGR overexpression and knockdown samples in Bel-7404 cells were performed for identifying potential mechanisms.Results: PIGR was significantly overexpressed in tumors compared to nontumors and in HCC serum peripheral blood mononuclear cells (PBMC) than in healthy individuals (all p < 0.05). In TCGA, PIGR was highly altered in 14% HCC patients. PIGR upregulation was significantly associated with poor disease-free survival (p < 0.05). More patients recurred/progressed in PIGR altered group compared to unaltered group (p < 0.01). PIGR was significantly higher in HCC patients with incomplete cirrhosis (p < 0.001) and established cirrhosis (p < 0.05). Fewer patients had N₀ lymph node stage in PIGR altered group than those in the unaltered group (p < 0.05). PIGR RNAseq revealed that ribosome signaling was the common pathway in PIGR overexpression and PIGR knockdown samples. RNAseq analysis indicated that RPL10, RPL10A, RPL12, RPL19, RPL36, RPL38, RPL41, RPL6, RPL8, RPS12, RPS14, RPS15A, RPS2, RPS27A and RPSA were significantly upregulated in PIGR overexpression group and downregulated in PIGR underexpression group (all p < 0.05).Conclusions: Aberrant PIGR was associated with HCC recurrence, and PIGR stimulated ribosome pathway might be a potential mechanism.