Artificial Downregulation of Ribosomal Protein L34 Restricts the Proliferation and Metastasis of Colorectal Cancer by Suppressing the JAK2/STAT3 Signaling Pathway.

The highly conserved ribosomal protein L34 (RPL34) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation, migration, invasion, and metastasis of CRC cells were significantly enhanced in vitro and in vivo. Furthermore, high expression of RPL34 accelerated cell cycle progression, activated the JAK2/STAT3 signaling pathway, and induced the epithelial-to-mesenchymal transition (EMT) program. Conversely, RPL34 silencing inhibited the CRC malignant progression. Utilizing immunoprecipitation assays, we identified the RPL34 interactor, the cullin-associated NEDD8-dissociated protein 1 (CAND1), which is a negative regulator of cullin-RING ligases. CAND1 overexpression reduced the ubiquitin level of RPL34 and stabilized RPL34 protein. CAND1 silencing in CRC cells resulted in a decrease in the ability of proliferation, migration, and invasion. CAND1 overexpression promoted CRC malignant phenotypes and induced EMT, and RPL34 knockdown rescued CAND1-induced CRC progression. In summary, our study indicates that RPL34 acts as a mediator, is stabilized by CAND1, and promotes proliferation and metastasis, in part, through the activation of the JAK2/STAT3 signaling pathway and induction of EMT in CRC.

Where is the optimal plane to mobilize the anterior rectal wall in female patients undergoing total mesorectal excision?

BACKGROUND: Since Heald proposed the total mesorectal excision (TME) procedure, the prognosis of patients with rectal cancer has been significantly improved. But Heald did not specifically describe the anterior surgical plane in female patients. And the surgical plane for mobilizing the anterior rectal wall during TME surgery in female patients remains controversial. AIM: To investigate the anatomy of the female pelvis and identify the optimal plane for mobilizing the anterior rectal wall. METHODS: We retrospectively collected surgical procedure videos and clinical data of female patients diagnosed with middle or low rectal cancer who underwent the TME procedure between January 2020 and October 2022 across six hospitals. The patients were divided into two groups based on the surgical approach used to mobilize the anterior rectal wall: The experimental group was to open the peritoneum at the lowest point of the peritonea reflection and enter the plane for mobilizing, while the control group was cut at 0.5-1 cm above the peritoneal reflection and enter another plan. Then, we compared the preoperative and postoperative information between the two groups. We also dissected and observed ten adult female pelvises to analyze the anatomic structure and compare the entry plane between the two approaches. Finally, we researched the pathological structure between the rectum and the vagina. RESULTS: Finally, 77 cases that met the criteria were included in our study. Our observations revealed that the experimental group underwent a smooth procedure, entering the plane amidst the mesorectal fascia and adventitia of the vagina, whereas the control group entered the plane between the vaginal adventitia and muscle layers. Compared to the control group, the experimental group showed a significant decrease in intraoperative bleeding [22.5 (19.5-50) mL vs 17 (5-20) mL, P = 0.01], as well as a shorter duration of hospitalization [9 (7-11.25) d vs 7 (6-10) d, P = 0.03]. Through the examination of surgical videos and cadaveric studies, we discovered that Denonvilliers' fascia is absent in females. Additionally, pathological sections further revealed the absence of Denonvilliers' fascia in females, with only loose connective tissue present between the mesorectal fascia and adventitia of the vagina. CONCLUSION: The plane amidst the mesorectal fascia and vaginal adventitia is the optimal surgical plane to mobilize the anterior rectal wall for female patients undergoing the TME procedure.

Centromere Protein A (CENPA) Regulates Metabolic Reprogramming in the Colon Cancer Cells by Transcriptionally Activating Karyopherin Subunit Alpha 2 (KPNA2).

The karyopherin α2 subunit gene (KPNA2), an oncogene, is involved in metabolic reprogramming in cancer. This study aimed to explore the function of KPNα2 in the growth and glycolysis in colon cancer (CC) cells. Genes from the Oncomine database that were differentially expressed in multiple CC types were screened. Bioinformatics analysis suggested that KPNA2 was highly expressed in CC, and consequently, high expression of KPNA2 was detected in the CC cell lines. Down-regulation of KPNA2 reduced viability and DNA-replication ability, and increased apoptosis of HCT116 and LoVo cells. It also reduced glucose consumption, extracellular acidification rate, and the ATP production in cells. Centromere protein A (CENPA) was confirmed as an upstream transcription activator of KPNA2. There was significant H3K27ac modification in the promoter region of KPNA2. CENPA primarily recruited histone acetyltransferase general control of amino acid synthesis (GCN)-5 to the promoter region of KPNA2 to induce transcription activation. Overexpression of either CENPA or GCN-5 blocked the role of short hairpin KPNα2 and restored growth and glycolysis in CC cells. To conclude, the findings from this study suggest that CENPA recruits GCN-5 to the promoter region of KPNA2 to induce KPNα2 activation, which strengthens growth and glycolysis in, and augments the development of, CC.

[Laparoscopic versus conventional open resection for colorectal cancer: a meta-analysis on recurrence].

OBJECTIVE: To compare the recurrence between laparoscopic resection and conventional open resection for colorectal cancer with meta-analysis. METHODS: Eligible articles were identified by searches of MEDLINE, EMBASE and the Cochrane database between January 1991 and January 2007 using the terms (laparoscopy, surgery, minimal invasive, colon, intestine, large, colectomy, colonic neoplasms, rectal neoplasms and randomized controlled trial). Prospective randomized clinical trials were eligible if they included patients with colorectal cancer treated by laparoscopic surgery versus open surgery followed-up by recurrence. Data were extracted from these trials by three independent reviewers. RESULTS: Ten trials with recurrence information of 2474 patients were involved. In the combined results, no significant difference in the OR for overall recurrence between the laparoscopic surgery and open surgery group was found (OR 0.95, 95%CI 0.76 to 1.19, P=0.64). Stratified by recurrence type, the combined results of the individual reports showed no significant differences for local recurrence (OR 0.79, 95%CI 0.50 to 1.25,P=0.32), distant metastasis (OR 0.89, 95%CI 0.62 to 1.28, P=0.54) and port-site or wound-site recurrence (OR 1.04,95%CI 0.21 to 5.27,P=0.96) between the two surgical techniques. CONCLUSION: The recurrence rates for patients with colorectal cancer treated by laparoscopic surgery do not differ significantly from those by open surgery. Longer follow up studies will further define outcomes comparing the two techniques in the treatment of colorectal cancer.

[Total mesorectal excision versus conventional radical surgery for rectal cancer: a meta analysis].

OBJECTIVE: To compare treatment outcomes of total mesorectal excision (TME) with those of conventional radical surgery (CRS) for rectal cancer. METHODS: Literature reviews were performed with key words, such as rectal cancer, total mesorectal excision, TME on all studies reported on TME versus CRS for rectal cancer between January 1986 to May 2006. According to the same screening criteria, 17 clinical studies were included in our systematic reviews. Two of our co-authors drew the details of trial design, characteristics of participants, results and so on from the studies included. Data analyses were performed by using RevMan 4.2. RESULTS: Sample volume in this Meta analysis was 5267 rectal cancer cases. Quality and quantity analyses were performed within all included studies, prospective studies (prospective nonrandomized studies and multicenter prospective nonrandomized studies) and retrospective studies. The results showed that postoperative survival rate was significantly increased [OR 1.81 (95%CI 1.55-2.11, P<0.00001), OR 1.79 (95%CI 1.49-2.15, P<0.00001) and OR 1.84 (95%CI 1.39-2.45, P<0.00001)] and local recurrence rate was significantly reduced [OR 0.35 (95%CI 0.29-0.43, P<0.00001), OR 0.41 (95%CI 0.32-0.53, P<0.00001) and OR 0.29 (95%CI 0.22-0.39, P<0.00001)] after TME was used. The results of all study analyses agreed with those from prospective studies analyses, in which postoperative mortality was significantly reduced [OR 0.51 (95%CI 0.32-0.87, P=0.007) and OR 0.56 (95%CI 0.33-0.94, P=0.04)] after TME treatment, meanwhile the results of retrospective study analyses indicated that there was no significant difference between TME group and CRS group in postoperative mortality [OR 0.39 (95%CI 0.14-1.10, P=0.07)]. TME was a risk factor for postoperative anastomotic leak according to the results of all included studies and prospective study analyses, but no difference between TME group and CRS group had been found [OR 1.24 (95%CI 0.84-1.83, P=0.29) OR 1.98 (95%CI 0.85-4.61, P=0.11)]. CONCLUSIONS: TME is still the standard operative technique for rectal cancer. As compared with CRS, TME results in lower postoperative local recurrence rate and higher survival rate.