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Background Natural orifice specimen extraction surgery for colorectal cancer has been introduced in order to reduce the abdominal incision, demonstrating major development potential in minimally invasive surgery. We are conducting this randomized controlled trial to assess whether robotic NOSES is non-inferior to traditional robotic-assisted surgery for patients with colorectal cancer in terms of primary and secondary outcomes. Method/design Accordingly, a prospective, open-label, randomized controlled, parallel-group, multicenter, and non-inferiority trial will be conducted to discuss the safety and efficacy of robotic natural orifice extraction surgery compared to traditional robotic-assisted surgery. Here, 550 estimated participants will be enrolled to have 80% power to detect differences with a one-sided significance level of 0.025 in consideration of the non-inferiority margin of 10%. The primary outcome is the incidence of surgical complications, which will be classified using the Clavien-Dindo system. Discussion This trial is expected to reveal whether robotic NOSES is non-inferior to traditional robotic-assisted surgery, which is of great significance in regard to the development of robotic NOSES for patients with colorectal cancer in the minimally invasive era. Furthermore, robotic NOSES is expected to exhibit superiority to traditional robotic-assisted surgery in terms of both primary and secondary outcomes. Trial registration ClinicalTrials.govNCT04230772. Registered on January 15, 2020.

Background Increasing evidence suggests that microRNAs (miRNAs) play critical roles in cancer progression. Therefore, investigating the function of miRNAs that are aberrantly expressed in gastric cancer (GC) and characterizing the involved underlying mechanism are essential for the treatment of gastric cancer. MiR-138-5p was found to be down-regulated in multiple cancers, which acted as a tumor suppressor in cancer progression; however, whether and how miR-138-5p regulates the malignant behaviors of GC has not been fully understood. Methods The level of miR-138-5p in GC tissues and cell lines was detected by RT-qPCR. The effects of miR-138-5p on the growth of GC cells were evaluated by the in vitro Cell Counting Kit-8 (CCK-8) assay, cell apoptosis, cell cycle analysis, wound-healing assay, and in vivo xenograft mice model. The targets of miR-138-5p were predicted using the miRDB online tool, confirmed by luciferase report assay and Western blot. Results MiR-138-5p was frequently decreased in GC tissues and cell lines. Decreased expression of miR-138-5p was significantly associated with the lymph node metastasis of GC patients. Overexpression of miR-138-5p suppressed GC cell proliferation, migration, increased cell apoptosis as well as inhibited the tumor growth in vivo. DEK oncogene was predicted as a potential target of miR-138-5p. MiR-138-5p bound the 3'-UTR of DEK and inhibited the level of DEK in GC cells. Restoration of DEK abrogated miR-138-5p overexpression-mediated suppression of GC cell proliferation and cell cycle arrest. Conclusion Our results demonstrated the anti-cancer role of miR-138-5p in GC by targeting DEK, which suggested miR-138-5p as a potential therapeutic target for the treatment of patient with GC.

Robotic rectal cancer resection with natural orifice extraction is a recently developed minimally invasive surgery used in the treatment of patients with rectal cancer. However, its safety and feasibility remain undiscussed and controversial. This study reported the clinical outcomes and prognostic factors pertaining to traditional robotic assisted rectal cancer resection alone against that of robotic rectal cancer resection with natural orifice extraction to provide a discussion on this issue. 49 patients who underwent robotic rectal cancer resection with natural orifice extraction and 49 matched patients who underwent conventional robotic assisted rectal cancer resection were systematically analyzed in this study. Regarding the baseline characteristics, after matching, no significant differences were observed between the natural orifice specimen extraction (NOSE) group and the robotic assisted rectal cancer resection (RARC) group. Patients in the NOSE group had a reduced visual analog scale (p p = 0.002) and suffered less surgical stress than those in the RARC group. Moreover, 4 complications were observed in the NOSE group and 7 complications in the RARC group with no significant difference (p = 0.337) in terms of complications. The two groups had a similar survival outcomes, where the 3-year overall survival (p = 0.738) and 3-year progression-free survival (p = 0.986) were all comparable between the two groups. Histological differentiation and T stage could be regarded as independent prognostic factors for 3-year overall survival and 3-year progression-free survival. Robotic rectal cancer resection with natural orifice extraction is a safe and feasible minimally invasive surgery for patients suffering from rectal cancer as it encompasses considerable several advantages. Histological differentiation and T stage may serve as independent prognostic factors for 3-year overall survival and 3-year progression-free survival.

Robotic- vs laparoscopic-assisted proctectomy for locally advanced rectal cancer based on propensity score matching: Short-term outcomes at a colorectal center in China

Introduction The evidence on efficacy of intravitreously administered Conbercept (IVC) monotherapy for diabetic macular degeneration was still limited. Methods A systematic review was conducted in November 2019 to summarize the current evidence on visual acuity (VA) changes with IVC monotherapy in the treatment of diabetic macular edema (DME) from Pubmed, ClinicalTrials.gov, EMbase, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chin VIP Information (VIP), and Chinese Biomedical Database (CBM). Retrospective or prospective clinical studies which used IVC injection for the treatment of DME were included. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA) and central macular thickness (CMT). A meta-regression was conducted to assess 1-year BCVA and CMT changes against numbers of injections. Results A total of 20 studies were included in current study. At 12-month follow-up, an overall increase of 0.67 logarithm of the minimum angle of resolution (logMAR) BCVA score [95% confidence interval (CI) 0.24–1.11; P = 0.003] and 1.03 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (95% CI 0.69–1.38; P

Purpose By comparing short- and long-term outcomes following totally robotic radical distal gastrectomy (TRDG) and robotic-assisted radical distal gastrectomy (RADG), we aimed to assess in which modus operandi patients will benefit more. Methods From January 2015 to May 2019, we included 332 patients undergone RADG (237) and TRDG (95). Based on the propensity score matching (PSM), inclusion and exclusion criteria, 246 patients were finally included in the propensity score-matched cohort including RADG group (164) and TRDG group (82). We then compared the short- and long-term outcomes following both groups. Results Propensity score-matched cohort revealed no significant differences in both groups. Intra-abdominal bleeding, time to pass flatus, postoperative activity time, length of incision hospital stays, and stress response were significantly less in TRDG group than in RADG group. We observed 30 complications in RADG group while 13 complications in TRDG group. There were no significant differences in TRDG group and RADG group in terms of operation time, time for anastomosis, proximal resection, distal resection margin, number of lymph node resection, and total hospitalization cost. Both 3-year overall survival and 3-year disease-free survival were comparable in both groups. Conclusions TRDG is a safe and feasible modus operandi profiting from short- and long-term outcomes compared with RADG. As surgeons improving their professional skills, TRDG could serve as the standard procedure for distal locally advanced gastric cancer with D2 lymphadenectomy.

MicroRNA (miR)‑744‑5p serves a pivotal role in the progression of multiple cancers; however, the function of miR‑744‑5p in colorectal cancer (CRC) remains largely unknown. In the present study, the effects of miR‑744‑5p on the progression of CRC were analyzed and the mechanisms involved were investigated. It was revealed that miR‑744‑5p was frequently downregulated in CRC tissues and cell lines. Overexpression of miR‑744‑5p significantly inhibited the proliferation, colony formation, and promoted the apoptosis of CRC cells. Bioinformatics analysis revealed that Septin 2 (SEPT2) was a potential target of miR‑744‑5p. miR‑744‑5p bound the 3'‑untranslated region (UTR) of SEPT2 and reduced the level of SEPT2 in CRC cells. A negative correlation between the expression of miR‑744‑5p and SEPT2 was observed in CRC tissues. Overexpression of SEPT2 counteracted the suppressive effect of miR‑744‑5p on the proliferation and apoptosis of CRC cells. Collectively, these data demonstrated the functional mechanism of miR‑744‑5p by targeting SEPT2, which suggested miR‑744‑5p as a potential target for the treatment of patients with CRC.

Gastric cancer is the most commonly occurring cancer with a rapidly increasing incidence rate worldwide. The underlying molecular mechanisms of gastric cancer require further investigation. MicroRNAs exhibit tissue sensitivity as tumor biomarkers that play a role by promoting tumor growth as oncogenes or tumor suppressor genes. We evaluated the effects of microRNA-12129 on gastric cancer and identified the underlying mechanisms of microRNA-12129. Quantitative real-time polymerase chain reaction was conducted to determine the expression levels of microRNA-12129 and sirtuin 1 in vivo and in vitro, and Western blot analysis was performed to detect sirtuin 1 at the protein level in gastric cancer cell lines. Cell proliferation and cell cycle progression were detected by Cell Counting Kit-8 assay and flow cytometry analysis, respectively. The potential targets of microRNA-12129 were predicted by bioinformatics analysis. The targets of microRNA-12129 were confirmed by luciferase reporter assay and rescue assay. We found that microRNA-12129 was downregulated in gastric cancer tissues and gastric cancer cell lines and was significantly associated with the prognosis of patients with gastric cancer. In addition, microRNA-12129 overexpression suppressed tumor cell proliferation and blocked cell cycle progression. Bioinformatics analysis and luciferase reporter assay suggested that sirtuin 1 was a target of microRNA-12129, and sirtuin 1 expression was negatively related to microRNA-12129. Restoration of sirtuin 1 partly reduced the inhibition of cell proliferation and cell cycle progression induced by microRNA-144. Our results collectively suggested that microRNA-12129 suppressed cell proliferation and cell cycle progression in gastric cancer by targeting sirtuin 1. These findings indicated that manipulation of microRNA-12129 expression could help develop a novel therapeutic strategy for gastric cancer.

Summary Protons are highly related to cell viability during physiological and pathological processes. Developing new probes to monitor the pH variation could be extremely helpful to understand the viability of cells and the cell death study. Carbonized polymer dots (CPDs) are superior biocompatible and have been widely applied in bioimaging field. Herein, a new type of extreme-pH suitable CPDs was prepared from citric acid and o-phenylenediamine (CA/oPD-CPDs). Due to the co-existence of hydrophilic and hydrophobic groups, CA/oPD-CPDs tend to aggregate in neutral condition with a dramatic decrease of fluorescence, but disperse well in both acidic and alkaline conditions with brighter emission. This specialty enables them to selectively illuminate lysosomes in cells. Moreover, CA/oPD-CPDs in the cytoplasm could serve as a sustained probe to record intracellular pH variation during apoptosis. Furthermore, CA/oPD-CPDs present a continuous fluorescence increase upon 2-h laser irradiation in living cells, underscoring this imaging system for long-term biological recording., Graphical Abstract, Highlights • CA/oPD-CPDs with extreme pH sensitivity through aggregation-dissociation process • Irradiation-enhanced CA/oPD-CPDs for mapping living cells in a real-time manner • CA/oPD-CPDs super-nanoparticles assembly to selectively visualize lysosomes • Mapping the spatial distribution of pH in living cells during apoptosis, Organic Chemistry; Optical Materials; Biotechnology

Reports in the field of robotic surgery for gastric cancer are increasing. However, studies only on patients with advanced gastric cancer (AGC) are lacking. This retrospective study was to compare the short-term outcomes of robotic-assisted distal gastrectomy (RADG) and laparoscopic-assisted distal gastrectomy (LADG) with D2 lymphadenectomy for AGC. From December 2014 to November 2019, 683 consecutive patients with AGC underwent mini-invasive assisted distal gastrectomy. Propensity-score matching (PSM) analysis was conducted to reduce patient selection bias. Short-term outcomes were compared between the two groups. The clinical features were well matched in the PSM cohort. Compared with the LADG group, the RADG group was associated with less operative blood loss, a lower rate of postoperative blood transfusion, less volume of abdominal drainage, less time to remove abdominal drainage tube, retrieved more lymph node, and lower rates of surgical complications and pancreatic fistula (P P > 0.05). This study suggests that RADG is a safe and feasible technique with better short-term outcomes than LADG for AGC.

Colorectal cancer (CRC) is one of most malignant tumors, mainly due to its high rate of metastasis and recurrence. The prognosis of CRC is difficult due to early CRC patients have no specific symptoms. Therefore, it is emergent to identify a biomarker for CRC prognosis. Cystatin SN (CST1) shows elevated expression in many tumors, but its role in CRCs is still unknown. Through immunohistochemistry analysis, we found that CST1 was upregulated in CRC samples. The survival analysis had demonstrated that high CST1 expression was closely associated with poor clinical status, providing that CST1 plays a role in CRC tumorigenesis. Furthermore, nomograms were generated using CST1 levels and other factors to evaluate survival of CRCs. We evaluated the reliabilities of these nomograms using an independent cohort of 141 CRC cases and found that high CST1 expression is linked to low survival, which is consistent with the clinical results. Thus, we could predict the survival of a CRC patient via these nomograms. In addition, the multivariate analysis identified CST1 as an independent prognostic factor for CRCs, providing CST1 as a biomarker for CRC prognosis. Taken together, our studies revealed a close relationship between CST1 and CRCs, suggesting that CST1 possibly acts as a marker for CRC prognosis and a target for CRC therapy.

Metastasis-associated recurrence is the main cause for the poor prognosis of hepatocellular carcinoma (HCC). However, the detailed molecular mechanisms underlying HCC metastasis remain elusive. Though some data indicated the oncogenic role of Sorcin in tumors, the prognostic value and biological role of Sorcin in HCC is still unknown. In this study, it demonstrated that Sorcin expression levels were significantly upregulated in HCC tumor tissues compared with matched adjacent nontumorous liver tissues and normal liver tissues, and such expression level correlated with HCC metastasis. High Sorcin expression was significantly correlated with aggressive clinicopathological characteristics such as multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P P in vitro, and facilitate HCC growth and metastasis in vivo. Mechanistically, Sorcin exerted its role by activating extracellular signal-regulated kinase (ERK) pathway and promoted metastasis by facilitating epithelial-mesenchymal transition (EMT) in HCC.

Purpose: To study the safety and efficacy of 1/3-dose verteporfin photodynamic therapy (PDT) for subacute central serous chorioretinopathy (CSC). Methods: In this case series, 59 eyes (59 patients) diagnosed with subacute CSC in Shenyang the 4th hospital from January 2014 to December 2015 were treated with 1/3-dose verteporfin PDT and followed up for at least 1 year. The symptoms and the diagnosed history were more than 3 months but shorter than 6 months. The central foveal thickness (CFT), neuroretinal thickness (NRT), height of subfoveal retinal fluid (SRF), and subfoveal choroidal thickness (SCT) were observed at baseline and after treated at 1, 2, 3, 6 and 12 months with EDI-OCT, Best-corrected visual acuity ( BCVA) was also studied at the same time. Results: After 1, 2, 3 and 6 months of 1/3-dose verteporfin PDT treatment, the BCVA improved significantly (P 0.05). The height of SRF changed significantly. There was no retinal pigment epithelium atrophy and choroidal neovascularization (CNV) in all cases after more than 12 months follow-up. Conclusion: Treatment of 1/3 dose verteporfin PDT could safely and effectively reduce expansion of choroidal vessel and choroidal choriocapillary, promoting absorbance of subretinal fluid for subacute CSC. 1/3-dose verteporfin PDT may be an alternative method to treat the subacute CSC.

Purpose: To evaluate the short-term efficacy of intravitreal anti-VEGF (Lucentis) and sub-tenon injection of triamcinolone acetonide for choroidal neovascularization (CNV) associated with multifocal choroiditis (MC). Methods: Eight eyes of 8 patients treated with intravitreal anti-VEGF and posterior sub-tenon injection of Triamcinolone Acetonide (TA) for subfoveal or juxtafoveal CNV associated with MC were retrospectively reviewed. Best corrected visual acuity (BCVA), results of fundus fluorescein angiography (FFA)/indocyanine green angiography (ICGA), optical coherence tomography (OCT) at baseline and 3, 6 months after treatment were compared. Results: All of the 8 patients showed significant improvement in BCVA at 3 and 6 months after treatment (P < 0.05). FFA/ICGA showed decrease or cessation of inflammation in 8 patients (100%). 7 patients (87.5%) had no significant active leakage while 1 patient (12.5%) had persistent leakage from the neovascular lesion at 3-month follow up. 6 months after treatment, no recurrence of inflammation occurred and no active leakage in all 8 patients. OCT showed reduced CNV area and alleviated edema. There are no severe treatment-related side effects expect slight eye pain during infusion in one patient. Intraocular pressure was all normal in follow up. Conclusion: Although the follow-up time and the number of patients in this study were limited, the use of intravitreal anti-VEGF combined with sub-tenon injection of TA was associated with improvement of visual acuity in patients with CNV secondary to MC. Further studies including a greater number of patients with longer follow up time are needed.

Diabetic retinopathy (DR) is a serious complication of diabetes and the most common metabolic disorder. Recently, long non-coding (lnc)RNAs have been identified as critical regulators of DR. Ribosomal protein SA pseudogene 52 (RPSAP52) is an oncogenic lncRNA expressed in pituitary tumors. The present study aimed to investigate the functions of RPSAP52 in DR. RPSAP52 levels in the plasma of diabetic patients with or without DR complication was detected. Luciferase reporter assays, RT-qPCR and western blotting were performed to detect the interaction between RPSAP52 and micro RNA (miR)-365. Moreover, expression vectors of RPSAP52 and Timp3, as well as miR-365 mimics were transfected into ARPE-19 cells exposed to high glucose and the apoptotic cells were detected. The results showed that RPSAP52 was downregulated in patients with DR compared with patients with diabetes without obvious complications. RPSAP52 directly interacted with miR-365, while overexpression of RPSAP52 and miR-365 did not affect the expression of one another. In addition, overexpression of RPSAP52 upregulated TIMP metallopeptidase inhibitor 3 (Timp3) in retinal pigment epithelial (RPE) cells. High glucose treatment led to downregulated RPSAP52 and Timp3, but upregulated miR-365 in RPE cells. Moreover, cell apoptosis analysis identified that overexpression of RPSAP52 and Timp3 led to a decreased apoptotic rate of RPE cells under high glucose treatment. Therefore, it was speculated that RPSAP52 may upregulate Timp3 by serving as the endogenous sponge of miR-365 in DR to suppress RPE cell apoptosis.

Previous studies have shown that Rho guanine nucleotide exchange factor 7 (ARHGEF7) is implicated in cytoskeleton remodelling, which is important for cell motility and invasiveness, and exhibits frequent high-level genetic amplification in metastatic lesions of colorectal adenocarcinoma. Therefore, it was hypothesized that ARHGEF7 may be involved in the metastasis of colorectal adenocarcinoma. In the present study, it was demonstrated that the expression level of ARHGEF7 was significantly upregulated in colorectal adenocarcinoma tumor tissues compared with matched nontumorous tissues, and its expression level correlated with colorectal adenocarcinoma metastasis. In vitro assays showed that the overexpression of ARHGEF7 in CRC cells significantly enhanced cell migration and invasion, whereas the knockdown of ARHGEF7 in colorectal adenocarcinoma cells significantly decreased cell migration and invasion. In vivo assays showed that the overexpression of ARHGEF7 in CRC cells facilitated tumor metastasis, whereas the knockdown of ARHGEF7 in CRC cells significantly inhibited tumor metastasis. Furthermore, it was demonstrated that ARHGEF7 promoted cell motility by regulating the actin cytoskeleton. Finally, according to ReMARK guidelines for reporting prognostic biomarkers in cancer, it was found that a high expression of ARHGEF7 was significantly correlated with lymph node, mesenteric and distant metastasis. Patients with colorectal adenocarcinoma with a high expression of ARHGEF7 had shorter disease-free survival (DFS) and shorter overall survival (OS) rates, compared with those with a low expression of ARHGEF7, as determined by the Kaplan-Meier method with a log-rank test. Cox regression analysis showed that a high expression of ARHGEF7 was an independent risk factor for DFS and OS rates in colorectal adenocarcinoma.

Metastasis-associated recurrence is the main cause for the poor prognosis of hepatocellular carcinoma (HCC). However, the detailed molecular mechanisms underlying HCC metastasis remain elusive. Though some data indicated the oncogenic role of Sorcin in tumors, the prognostic value and biological role of Sorcin in HCC is still unknown. In this study, it demonstrated that Sorcin expression levels were significantly upregulated in HCC tumor tissues compared with matched adjacent nontumorous liver tissues and normal liver tissues, and such expression level correlated with HCC metastasis. High Sorcin expression was significantly correlated with aggressive clinicopathological characteristics such as multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P

Colorectal cancer (CRC) is among the cancers with the highest incidence globally, and it currently ranks as the fourth leading cause of cancer-related deaths worldwide. Novel strategies for the treatment of advanced CRC are urgently needed, and adoptive transfer of allogeneic natural killer (NK) cells represents an attractive option. In this study, we successfully expanded NK cells from umbilical cord blood (UCB) with membrane-bound interleukin (IL)-21, termed eUCB-NK cells. eUCB-NK cells efficiently lysed CRC cell lines in vitro and secreted significantly higher levels of interferon-γ, tumor necrosis factor-α, granulocyte-macrophage colony stimulating factor, and chemokine ligand 3 compared with IL-2-stimulated NK cells. Adoptive transfer of these NK cells significantly inhibited the growth of HT29 xenografts, whereas LoVo tumors were not effectively controlled with eUCB-NK cells. Higher numbers of NK cells inside HT29 tumors, not seen in LoVo tumors, might contribute to the differences in response to eUCB-NK cells. Bevacizumab increased extravasation of adoptively transferred NK cells into LoVo tumors and improved the therapeutic activity of eUCB-NK cells. These results justify clinical translation of UCB-derived NK cell-based therapeutics, used alone or in combination with bevacizumab, as a novel treatment option for patients with CRC.

Supplemental Digital Content is available in the text, Rationale: Synchronous double malignancies, including carcinoma of the ampulla of Vater and rectal carcinoma, are generally uncommon occurrences in the gastrointestinal tract. Patient concerns: The present study report a case of a 37-year-old man who was incidentally found to suffer from carcinoma of the ampulla of Vater and rectal carcinoma. Diagnoses: The duodenoscopy was performed and revealed an ulcerated and bulky ampulla of Vater, the biopsy from which revealed a moderate-differentiated adenocarcinoma, A local hospital colonoscopy confirmed a tumor located in rectal 7 cm from the anal margin and biopsy-confirmed poorly differentiated adenocarcinoma. Interventions: About such patient treatment, both open and laparoscopic surgery are restricted because of operation complexity, large injury, and poor cosmetic effect. surgery performed using Da Vinci robotic surgical system (DVSS). Outcomes: No evidence of recurrence or relapses was found in the first year after surgery. Lessons: Although sporadic double malignancies are uncommon, they should be considered when evaluating cancer patients. Complex surgery performed by robotic surgery may became surgeon's preferred treatment modality.

Partitioning defective 3–like protein is a novel cell polarity protein. Recently, partitioning defective 3–like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3–like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3–like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues. We found that colorectal cancer tissues had much stronger partitioning defective 3–like protein immunoreactivity than normal tissues, and colorectal cancer patients with positive partitioning defective 3–like protein expression were characterized with higher cancer stages, metastasis, poor tumor differentiation, larger tumor size, as well as high levels of colorectal cancer markers carcinoembryonic antigen and cancer antigen 19-9. Besides, partitioning defective 3–like protein overexpression was independently predictive of lower survival rate in colorectal cancer patients, even after adjusting the influence of cofactors. Moreover, we also found that partitioning defective 3–like protein was associated with rapid growing colorectal cancer, while knockdown of partitioning defective 3–like protein expression largely inhibited cancer cell proliferation. Our study provided the first evidence that partitioning defective 3–like protein was overexpressed in colorectal cancer and associated with disease malignancy. Also, partitioning defective 3–like protein may serve as a promising prognostic marker and a potential therapeutic target for colorectal cancer treatment. Further study is necessary to understand the regulatory mechanism of partitioning defective 3–like protein in colorectal cancer and the feasibility of its application in clinic.

Totally robotic right hemicolectomy (TRRH) is a novel alternative surgical method used for the treatment of colon cancer. The aim of this study was to compare both the short-and long-term outcomes of TRRH and robotic-assisted right hemicolectomy (RARH) for the treatment of colon cancer.We pe

Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinase B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC.

Altered expression of flotillin-2 (FLOT2) has been identified in certain types of cancer, including breast cancer and melanoma; however, to the best of our knowledge, the association between the FLOT2 expression level and colorectal cancer (CRC) remains to be determined. The aim of the present study was to investigate the clinical and prognostic significance of FLOT2 in CRC. The expression of FLOT2 was determined in seven CRC cell lines and one normal colon cell line, and it was identified that FLOT2 was increased in CRC cell lines, suggesting that FLOT2 exhibited an association with CRCs. In addition, FLOT2 protein levels were investigated in primary CRC tissues and corresponding non-cancerous colon tissues from 8 patients. Compared with non-cancerous tissues, FLOT2 protein was apparently upregulated in CRC tissues. To validate this result, an immunohistochemistry assay was performed and it was identified that FLOT2 levels were increased in CRC tissues. Clinical analysis identified that increased expression of FLOT2 was associated with the depth of invasion, lymph node metastasis, distant metastasis and American Joint Committee on Cancer stage of CRCs. Furthermore, multivariate analysis using the Cox regression model indicated that increased FLOT2 expression was an independent prognostic factor in patients with CRC (P=0.013). Taken together, the results of the present study suggest that overexpression of FLOT2 contributes to the progression of CRC and indicate that FLOT2 is a novel target for the treatment of CRC.