Digestive system involvement of infections with SARS-CoV-2 and other coronaviruses: Clinical manifestations and potential mechanisms.

Although coronavirus (CoV) infection is often characterized by respiratory symptoms, the virus can also result in extrapulmonary symptoms, especially the symptoms related to the digestive system. The outbreak of coronavirus disease 2019 (COVID-19) is currently the world's most pressing public health threat and has a significant impact on civil societies and the global economy. The occurrence of digestive symptoms in patients with COVID-19 is closely related to the development and prognosis of the disease. Moreover, thus far, there are no specific antiviral drug or vaccine approved for the treatment or prevention of COVID-19. Therefore, we elaborate on the effects of CoVs on the digestive system and the potential underlying mechanisms.

Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice.

Sevoflurane, the most commonly used inhaled anesthetic in pediatric anesthesia, has been reported to induce cognitive impairment in developing brain in preclinical and clinical settings. However, the mechanism and therapeutic measures of this developmental neurotoxicity need to be further investigated. Resveratrol, a natural polyphenolic agent, has been reported to improve cognitive function in neurological disorders and aging models through anti-inflammatory activity. However, its effect on sevoflurane-induced cognitive impairment in developing mice remains unknown. The present study was designed to investigate the therapeutic potential of resveratrol on sevoflurane-induced cognitive impairment. Six-day-old mice received anesthesia with 3% sevoflurane 2 h daily on postnatal days (P) 6, P7 and P8. About 100 mg/kg resveratrol were intraperitoneally administered for 6 consecutive days to neonatal mice before anesthesia. Sevoflurane exposure significantly suppressed the expression of Sirtuin 1 (SIRT1) and activated microglia in hippocampi. Furthermore, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were markedly increased after sevoflurane exposure. Strikingly, resveratrol pretreatment ameliorated sevoflurane-induced SIRT1 inhibition and microglial activation. Of note, resveratrol reversed sevoflurane-induced imbalance of M1/M2 microglia ratio revealed by increasing mRNA level of clusters of differentiation 206 (CD206) and decreasing mRNA levels of clusters of differentiation 86 (CD86) and suppressor of cytokine signaling 3 (SOCS3). Consequently, sevoflurane-induced cognitive impairment in developing mice was ameliorated by resveratrol pretreatment. Taken together, repeated sevoflurane exposure to the developing brain resulted in SIRT1 inhibition, NF-κB acetylation, and microglial activation. Resveratrol pretreatment ameliorated cognitive impairment in developing mice received sevoflurane exposure by modulating SIRT1-NF-κB pathway in microglia. In this regard, our findings open novel directions to explore promising therapeutic targets for preventing the developmental neurotoxicity of sevoflurane.

Downregulation of DLGAP1-Antisense RNA 1 Alleviates Vascular Endothelial Cell Injury Via Activation of the Phosphoinositide 3-kinase/Akt Pathway Results from an Acute Limb Ischemia Rat Model.

OBJECTIVE: This study aimed to investigate the effect of long non-coding RNA (lncRNA) DLGAP1 antisense RNA 1 (DLGAP1-AS1) on vascular endothelial cell (VEC) injury via the phosphoinositide 3-kinase (PI3K)/Akt pathway in rat models of acute lower limb ischaemia-reperfusion (I/R). METHODS: Differentially expressed lncRNAs related to I/R were screened using the gene expression omnibus database. Acute lower limb I/R models were induced in male Wistar rats, in which the regulatory mechanisms of DLGAP1-AS1 silencing were analysed after the treatment of small interfering RNA (siRNA) against DLGAP1-AS1 or an inhibitor of the PI3K/Akt pathway. The relationship between DLGAP1-AS1 and the PI3K/Akt pathway was analysed. The levels of tumour necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1), as well as malondialdehyde (MDA) concentration and creatine kinase (CK) activity, were measured. The number of circulating endothelial cells (CECs) and apoptosis of VECs were identified. RESULTS: Microarray based analysis indicated that DLGAP1-AS1 was highly expressed in I/R, which was further confirmed by detection of expression in rat models of acute lower limb I/R. Notably, the treatment of siRNA against DLGAP1-AS1 led to the activation of the PI3K/Akt pathway. In response to siRNA against DLGAP1-AS1, the levels of TNF-α and VCAM-1 were decreased, and MDA concentration and CK activity was downregulated. Reduced CEC numbers and suppressed VEC apoptosis were also observed. CONCLUSION: DLGAP1-AS1 silencing could further suppress the oxidative stress, exert an anti-apoptosis effect, and reduce inflammatory reaction, whereby VEC injury is alleviated by activation of the PI3K/Akt pathway in rats with acute lower limb I/R.

Nano-Curcumin Simultaneously Protects the Blood-Brain Barrier and Reduces M1 Microglial Activation During Cerebral Ischemia-Reperfusion Injury.

Oxidative stress and inflammation are two important pathophysiological mechanisms that arouse neuronal apoptosis and cerebral damage after ischemia/reperfusion (I/R) injury. Here, we hypothesized that curcumin-encapsulated nanoparticles (NPcurcumin) could reduce oxidative stress and inflammation in the ischemic penumbra via protecting the blood-brain barrier (BBB) and inhibiting M1-microglial activation. Under oxidative stress conditions in vitro, we found that NPcurcumin protected microvascular endothelial cells against oxidative stress and reduced BBB permeability. In vivo, NPcurcumin could cross the BBB and accumulate in the ischemic penumbra. At 3 d after I/R injury, NPcurcumin inhibited the increase in MMP-9, attenuated the decrease in occludin and zona occluden-1, and maintained BBB integrity. NPcurcumin effectively reduced the number of activated M1 microglia and weakened the increase in TNF-α and IL-1ß. Furthermore, NPcurcumin also reduced the infarct size and improved function recovery.

Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.

The role and gene expression profile of SOCS3 in colorectal carcinoma.

SOCS3 has been postulated to play a role in the occurrence and progression of malignancies. However, the relationship of SOCS3 with colorectal carcinoma remains poorly understood. The purpose of the study was to explore the role of SOCS3 in colorectal carcinoma and its underlying mechanisms. Protein and mRNA expression of SOCS3 in colorectal carcinoma and normal colorectal mucosa was detected using immunohistochemistry and real-time quantitative PCR. SOCS3 expression was significantly lower in colorectal carcinoma tissue than in normal colorectal mucosa, and was negatively correlated with tumor invasion depth, lymph node metastasis, differentiation degree, and TNM stage. A stably transfected colorectal carcinoma cell line (8348SOCS3) with high expression of SOCS3 was established. The effects of SOCS3 overexpression on the growth, proliferation, invasion and tumor formation of colorectal carcinoma cells were examined by CCK-8 assay, transwell method and tumorigenicity assays in nude mice. Then we found SOCS3 overexpression significantly decreased proliferation and invasion capability of 8348 cells in vitro and in vivo. Furthermore, the effect of SOCS3 overexpression on the gene expression profile of colorectal carcinoma cells was analyzed using human genome arrays. The results revealed 369 genes that were differentially expressed in 8348SOCS3 cells. 193 genes was significantly increased and 176 genes was significantly decreased. Bioinformatics analysis demonstrated that high SOCS3 expression affected multiple signaling pathways in colorectal carcinoma including TGF-ß/Smads, NF-κB, and HIF-MAPK pathways. Especially for the TGF-ß/Smads pathways, high SOCS3 expression could inhibit TGF-ß1 expression and activate Smad4 expression. These data suggested that low expression of SOCS3 was associated with the occurrence and progression of colorectal carcinoma. SOCS3 protein may be a useful indicator for malignancy and prognosis of colorectal carcinoma and also a new target for gene therapy.

Protecting neurons from cerebral ischemia/reperfusion injury via nanoparticle-mediated delivery of an siRNA to inhibit microglial neurotoxicity.

Complement component C3 (C3) plays a central role in microglial neurotoxicity following cerebral ischemia/reperfusion (I/R) injury. In this study, we focused on the role of nanoparticles loaded with C3 siRNA (NPsiC3) in inhibiting microglial neurotoxicity after brain (I/R) injury. NPsiC3 inhibited the hypoxia/re-oxygenation-induced increase in C3 expression in microglia in vitro. Importantly, treatment with NPsiC3 decreased C3b deposition on neurons and reduced microglia-mediated neuronal damage under hypoxia/re-oxygen conditions. Nanoparticles could effectively deliver C3-siRNA from the blood into ischemic penumbra across the blood-brain barrier (BBB) and significantly decrease C3 expression in microglia and ischemic brain tissue, while reducing the number of infiltrating inflammatory cells and the concentration of pro-inflammatory factors in the penumbra. Furthermore, NPsiC3 also prevented neuronal apoptosis, reduced the volume of the ischemic zone, and substantially improved functional recovery after I/R injury. Therefore, the NPsiC3-induced inhibition of microglial neurotoxicity represents a novel therapeutic strategy for treating brain I/R injury.

Restoring anti-tumor functions of T cells via nanoparticle-mediated immune checkpoint modulation.

The core purpose of cancer immunotherapy is the sustained activation and expansion of the tumor specific T cells, especially tumor-infiltrating cytotoxic T lymphocytes (CTLs). Currently, one of the main foci of immunotherapy involving nano-sized carriers is on cancer vaccines and the role of professional antigen presenting cells, such as dendritic cells (DCs) and other phagocytic immune cells. Besides the idea that cancer vaccines promote T cell immune responses, targeting immune inhibitory pathways with nanoparticle delivered regulatory agents such as small interfering RNA (siRNA) to the difficultly-transfected tumor-infiltrating T cells may provide more information on the utility of nanoparticle-mediated cancer immunotherapy. In this study, we constructed nanoparticles to deliver cytotoxic T lymphocyte-associated molecule-4 (CTLA-4)-siRNA (NPsiCTLA-4) and showed the ability of this siRNA delivery system to enter T cells both in vitro and in vivo. Furthermore, T cell activation and proliferation were enhanced after NPsiCTLA-4 treatment in vitro. The ability of direct regulation of T cells of this CTLA-4 delivery system was assessed in a mouse model bearing B16 melanoma. Our results demonstrated that this nanoparticle delivery system was able to deliver CTLA-4-siRNA into both CD4(+) and CD8(+) T cell subsets at tumor sites and significantly increased the percentage of anti-tumor CD8(+) T cells, while it decreased the ratio of inhibitory T regulatory cells (Tregs) among tumor infiltrating lymphocytes (TILs), resulting in augmented activation and anti-tumor immune responses of the tumor-infiltrating T cells. These data support the use of potent nanoparticle-based cancer immunotherapy for melanoma.

Laparoscopic resection of lower rectal cancer with telescopic anastomosis without abdominal incisions.

AIM: To assess laparoscopic radical resection of lower rectal cancer with telescopic anastomosis through transanal resection without abdominal incisions. METHODS: From March 2010 to June 2014, 30 patients (14 men and 16 women, aged 36-78 years, mean age 59.8 years) underwent laparoscopic radical resection of lower rectal cancer with telescopic anastomosis through anus-preserving transanal resection. The tumors were 5-7 cm away from the anal margin in 24 cases, and 4 cm in six cases. In preoperative assessment, there were 21 cases of T1N0M0 and nine of T2N0M0. Through the middle approach, the sigmoid mesentery was freed at the root with an ultrasonic scalpel and the roots of the inferior mesenteric artery and vein were dissected, clamped and cut. Following the total mesorectal excision principle, the rectum was separated until the anorectal ring reached 3-5 cm from the distal end of the tumor. For perineal surgery, a ring incision was made 2 cm above the dentate line, and sharp dissection was performed submucosally towards the superior direction, until the plane of the levator ani muscle, to transect the rectum. The rectum and distal sigmoid colon were removed together from the anus, followed by a telescopic anastomosis between the full thickness of the proximal colon and the mucosa and submucosal tissue of the rectum. RESULTS: For the present cohort of 30 cases, the mean operative time was 178 min, with an average of 13 positive lymph nodes detected. One case of postoperative anastomotic leak was observed, requiring temporary colostomy, which was closed and recovered 3 mo later. The postoperative pathology showed T1-T2N0M0 in 19 cases and T2N1M0 in 11 cases. Twelve months after surgery, 94.4% patients achieved anal function Kirwan grade 1, indicating that their anal function returned to normal. The patients were followed up for 1-36 mo, with an average of 23 mo. There was no local recurrence, and 17 patients survived for > 3 years (with a survival rate of 100%). CONCLUSION: Laparoscopic radical resection of lower rectal cancer with telescopic anastomosis through transanal resection without abdominal incisions is safe and feasible.

Co-delivery of all-trans-retinoic acid and doxorubicin for cancer therapy with synergistic inhibition of cancer stem cells.

Combination treatment through simultaneous delivery of two or more drugs with nanoparticles has been demonstrated to be an elegant and efficient approach for cancer therapy. Herein, we employ a combination therapy for eliminating both the bulk tumor cells and the rare cancer stem cells (CSCs) that have a high self-renewal capacity and play a critical role in cancer treatment failure. All-trans-retinoic acid (ATRA), a powerful differentiation agent of cancer stem cells and the clinically widely used chemotherapy agent doxorubicin (DOX) are simultaneously encapsulated in the same nanoparticle by a single emulsion method. It is demonstrated that ATRA and DOX simultaneous delivery-based therapy can efficiently deliver the drugs to both non-CSCs and CSCs to differentiate and kill the cancer cells. Differentiation of CSCs into non-CSCs can reduce their self-renewal capacity and increase their sensitivity to chemotherapy; with the combined therapy, a significantly improved anti-cancer effect is demonstrated. Administration of this combinational drug delivery system can markedly augment the enrichment of drugs both in tumor tissues and cancer stem cells, prodigiously enhancing the suppression of tumor growth while reduce the incidence of CSC in a synergistic manner.

Combination therapy with epigenetic-targeted and chemotherapeutic drugs delivered by nanoparticles to enhance the chemotherapy response and overcome resistance by breast cancer stem cells.

Aberrant DNA hypermethylation is critical in the regulation of renewal and maintenance of cancer stem cells (CSCs), which represent targets for carcinogenic initiation by chemical and environmental agents. The administration of decitabine (DAC), which is a DNA hypermethylation inhibitor, is an attractive approach to enhancing the chemotherapeutic response and overcoming drug resistance by CSCs. In this study, we investigated whether low-dose DAC encapsulated in nanoparticles could be used to sensitize bulk breast cancer cells and CSCs to chemotherapy. In vitro studies revealed that treatment with nanoparticles loaded with low-dose DAC (NPDAC) combined with nanoparticles loaded with doxorubicin (NPDOX) better reduced the proportion of CSCs with high aldehyde dehydrogenase activity (ALDH(hi)) in the mammospheres of MDA-MB-231 cells, and better overcame the drug resistance by ALDH(hi) cells. Subsequently, systemic delivery of NPDAC significantly down-regulated the expression of DNMT1 and DNMT3b in a MB-MDA-231 xenograft murine model and induced increased caspase-9 expression, which contributed to the increased sensitivity of the bulk cancer cells and CSCs to NPDOX treatment. Importantly, the combined treatment of NPDAC and NPDOX resulted in the lowest proportion of ALDH(hi) CSCs and the highest proportion of apoptotic tumor cells, and the best tumor suppressive effects in inhibiting breast cancer growth.

The Owen value of stochastic cooperative game.

We consider stochastic cooperative game and give it the definition of the Owen value, which is obtained by extending the classical case. Then we provide explicit expression for the Owen value of the stochastic cooperative game and discuss its existence and uniqueness.

Expression of HAX-1 in human colorectal cancer and its clinical significance.

Colorectal cancer (CRC) remains one of the most common cancers worldwide. HS1-associated protein X-1 (HAX-1) has been highlighted as an important marker in many types of cancers. However, little is known about the role of HAX-1 in CRC. The aim of this study was to analyze the correlation of HAX-1 expression with the clinicopathological features of CRC. The protein and mRNA levels of HAX-1 were examined by immunohistochemistry (IHC) and real-time quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) in CRC tissues and adjacent noncancerous tissues. Survival curves were made with follow-up data. The relations of the prognosis with clinical and pathological characteristics were analyzed. Using IHC and RT-qPCR, we showed that HAX-1 expression was significantly higher in CRC tissues than in adjacent noncancerous tissues (P < 0.05). High HAX-1 expression was significantly associated with lymph node metastasis (P = 0.034) and tumor (T) node (N) metastasis (M) stage (P = 0.028) of patients with CRC. The Kaplan-Meier survival curves indicated that overall survival was significantly worse in CRC patients with HAX-1 overexpression. Multivariate analysis showed that high HAX-1 expression was an independent predictor of overall survival. In conclusion, our data for the first time provide a basis for the concept that overexpression of HAX-1 may contribute to the malignant progression of CRC and predict poor prognosis for patients with this disease. HAX-1 might be an important marker for tumor progression and prognosis, as well as a potential therapeutic target of CRC.

Role of GSK-3ß in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats.

This study investigated the role of glycogen synthase kinase-3ß (GSK-3ß) in isoflurane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride (LiCl, 100 mg/kg) and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-3ß was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Morris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3ß was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflurane anesthesia increased mRNA levels of TNF-α, IL-1ß and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiCl, a non-selective inhibitor of GSK-3ß. Additionally, we discovered that LiCl alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-3ß in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-κB p65 (Lys310). In conclusion, these results suggested that GSK-3ß is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.

Anus-preserving rectectomy via telescopic colorectal mucosal anastomosis for low rectal cancer: experience from a Chinese cohort.

AIM: To investigate the safety and efficacy of anus-preserving rectectomy via telescopic colorectal mucosal anastomosis (TCMA) for low rectal cancer. METHODS: From August 1993 to October 2012, 420 patients including 253 males and 167 females with low rectal cancer underwent transabdominal and transanal anterior resection, followed by TCMA. The distance between the anus and inferior margin of the tumor ranged from 5 to 7 cm, and was 5 cm in 6 patients, 6 cm in 127, and 7 cm in 287 patients. Tumor-node-metastasis staging showed that 136 patients had stage I, 252 had stage II and 32 had stage III. Fifty-six patients with T3 or over received preoperative neoadjuvant chemoradiotherapy. RESULTS: The postoperative follow-up rate was 91.9% (386/420) with a median time of 6.4 years. All 420 patients underwent radical resection. No postoperative death occurred. Postoperative complications included anastomotic leakage in 13 (3.1%) patients and anastomotic stenosis in 7 (1.6%). The local recurrence rate after surgery was 6.2%, the hepatic metastasis rate was 13.2% and the pulmonary metastasis rate was 2.3%. The 5-year survival rate was 74.0% and the disease-free survival rate was 71.0%. Kirwan classification showed that continence was good in 94.4% of patients with stage I when scored 12 mo after resection. CONCLUSION: TCMA for patients with low rectal cancer leads to better quality of life and satisfactory defecation function, and lowers anastomotic leakage occurrence, and might be one of the safe operative procedures in anus-preserving rectectomy.

Minocycline mitigates isoflurane-induced cognitive impairment in aged rats.

Postoperative cognitive dysfunction (POCD) is a severe neurological sequela that occurs in individuals who have undergone anesthesia and surgery, especially in the geriatric surgical population. Although it is known that isoflurane exposure impairs cognitive function in aged rodents, there are few clinical interventions for the prophylaxis and treatment of this disorder. Minocycline, a derivative of tetracycline, produces neuroprotection from several neurodegenerative diseases. Therefore, we set out to investigate the effects of minocycline pretreatment on isoflurane-induced cognitive impairment in aged rats. We found that pretreatment with minocycline remarkably alleviated isoflurane-induced cognitive dysfunction and inhibited the isoflurane-induced over expression of TNF-α, IL-1ß, and IL-6, possibly by inhibiting the degradation of IκBα. In addition, minocycline downregulated the isoflurane-induced increase in the protein levels of cleaved caspase 3 and bax, and upregulated the bcl-2 protein level. These findings highlight the beneficial role of minocycline in preventing isoflurane-induced cognitive impairment and suggested that minocycline can be used as a clinical treatment to mitigate the cognitive impairment induced by isoflurane in elderly patients.

[Expression and clinical significance of Claudin-1 and Claudin-4 in colorectal cancer tissues].

OBJECTIVE: To investigate the expression of tight junction protein Claudin-1 and Claudin-4 in colorectal cancer tissues and its clinical significance. METHODS: Immunohistochemical staining detected the expression of tight junction protein Claudin-1 and Claudin-4 in 60 cases of colorectal cancer and 20 normal colorectal mucosa tissue. The clinical significance was analyzed. RESULTS: The positive rates of Claudin-1 and Claudin-4 in colorectal cancer tissues were 76.6%(46/60) and 85.0%(51/60), significantly higher than 20.0% (4/20) and 30.0%(6/20) in the normal colorectal mucosa(both P<0.01). The positive rates of Claudin-1 and Claudin-4 were associated with tumor differentiation degree, lymph node metastasis and TNM staging(all P<0.05). CONCLUSIONS: The high expression of the Claudin-1 and Claudin-4 may play a promoting role in colorectal cancer development and progression. Claudin-1 and Claudin-4 may become prognostic markers of colorectal cancer.

Silencing phospholipid scramblase 1 expression by RNA interference in colorectal cancer and metastatic liver cancer.

BACKGROUND: Phospholipid scramblase 1 (PLSCR1) not only participates in the transbilayer movement of phospholipids, but also plays a role in the pathogenesis and progression of cancers. The present study aimed to evaluate the effect of silencing PLSCR1 expression by RNA interference in colorectal cancer (CRC) and metastatic liver cancer. METHODS: The expression of PLSCR1 in CRC and metastatic liver cancer samples was assessed by immunohistochemistry. The cultured cells with the highest expression were selected for subsequent experiments. We designed three siRNA oligonucleotide segments targeted at PLSCR1. Successful transfection was confirmed. The biological behavior of the cells in proliferation, adhesion, migration and invasion was determined. RESULTS: PLSCR1 protein expression increased significantly in the majority of CRC and metastatic liver cancer samples compared with normal samples. Lovo cells had the highest expression of PLSCR1. The siRNA-390 oligonucleotide segment had the best silencing effect. After transfection, Lovo cell proliferation was significantly inhibited compared with the controls in the MTT assay. Laminin and fibronectin adhesion assays showed Lovo cell adhesion was also significantly inhibited. In the migration assay, the number of migrating cells in the PLSCR1 siRNA-390 group was 50+/-12, significantly lower than the number in the siRNA-N group (115+/-28) and in the control group (118+/-31). In an invasion test, the number of invading cells in the PLSCR1 siRNA-390 group was 60+/-18, significantly lower than that in the siRNA-N group (97+/-26) and the control group (103+/-24). CONCLUSIONS: PLSCR1 is overexpressed in CRC and metastatic liver cancer. Silencing of PLSCR1 by siRNA inhibits the proliferation, adhesion, migration and invasion of Lovo cells, which suggests that PLSCR1 contributes to the tumorigenesis and tumor progression of CRC. PLSCR1 may be a potential gene therapy target for CRC and associated metastatic liver cancer.