Background Long noncoding RNAs (lncRNAs) play critical factors in tumor progression and are ectopically expressed in malignant tumors. Until now, lncRNA PTTG3P biological function in colorectal cancer (CRC) needs further to be clarified. Methods qRT-PCR was used to measure the PTTG3P level and CCK-8, glucose uptake, lactate assay, ATP assay, ECAR assay, and xenograft mice model were adopted to evaluate the glycolysis and proliferation, and macrophage polarization were determined in CRC cells. Xenograft experiments were utilized to analyze tumor growth. Results Ectopic expression of PTTG3P was involved in CRC and related to dismal prognosis. Through gain-of-function and loss-of-function approaches, PTTG3P enhanced cell proliferation and glycolysis through YAP1. Further, LDHA knockdown or glycolysis inhibitor (2-DG,3-BG) recovered PTTG3P-induced proliferation. And PTTG3P overexpression could facilitate M2 polarization of macrophages. Silenced PTTG3P decreased the level of inflammatory cytokines TNF-α, IL-1β, and IL-6, and low PTTG3P expression related with CD8+ T, NK, and TFH cell infiltration. Besides, HIF1A could increase PTTG3P expression by binding to the PTTG3P promoter region. Conclusions Hypoxia-induced PTTG3P contributes to glycolysis and M2 phenotype of macrophage, which proposes a novel approach for clinical treatment.
Background Pseudogene has emerged as key regulators of important biological processes involved in human cancers. However, the PTTG3P biological function in colorectal cancer (CRC) needs further to be clarified. Methods qRT-PCR was adopted to measure the PTTG3P expression in different cell line and CRC tissues. Cellular localization of PTTG3P was detected by subcellular fractionation assay. In vitro and in vivo experiments were carried out to explore the bioeffect of PTTG3P in CRC cells. Chromatin immunoprecipitation (ChIP), luciferase assay and RIP were explored to certify the direct binding of PTTG3P and microRNA. Results PTTG3P was upregulated in CRC and closely related to poor prognosis. Through gain and loss of function approaches, PTTG3P facilitated proliferation and glycolysis through YAP1, and glycolysis inhibitor (2-DG,3-BG) and LDHA knockdown could rescue cell proliferation and tumorigenesis. Mechanically, miR-1271-5p modulates PTTG3P expression and miR-1271-5p mimics could recover the PTTG3P function. Also HIF1A increased PTTG3P expression in both normoxia and hypoxia conditions by ameliorating miR-1271-5p expression. In addition, silencing PTTG3P decreases the level of inflammatory cytokines TNF-α, IL-1β and IL-6, and low PTTG3P expression relates with CD8+ T, NK and TFH cells infiltration. Conclusions Our findings verified the oncogenic function of PTTG3P in assisting the cell proliferation and glycolysis, demonstrating the pivotal roles of HIF1A/miR-1271-5p/lncRNA PTTG3P/YAP1 in CRC progression, which proposes a novel approach for clinical treatment.
Background: To evaluate the efficacy and safety between wait and see strategy (WS) and surgery of rectal cancer patients with cCR/near-cCR response after neoadjuvant chemoradiotherapy.Methods: We searched PubMed, Cochrane Library, CNKI(China National Knowledge Infrastructure) and Wanfang databases to compare wait and see strategy with surgery for rectal cancer with cCR/near-cCR response after neoadjuvant chemoradiotherapy up to January 2020. We collected the data of local recurrence, distant metastasis, cancer related death, overall survival and diseasr-free survival and compared the advantages and disadvantages of the two groups.Results: 14 English studies with 3932 patients were included. There were 700 patients in WS group and 3232 patients in surgical group. WS group had higher local recurrence rate than surgery group(OR:3.55, 95% CI :2.35 to 5.36, P<0.001). WS group had better 2-year DFS(OR:0.74, 95% CI :0.56 to 0.96, P=0.03) and 2-year OS (OR:0.38, 95% CI :0.28 to 0.52, P<0.001) than surgery group. Subgroup analysis of WS group and radical surgery group also obtained the similar results. Eastern studies also supported the conclusion. There was no significant difference of other data between the two groups.Conslusion: Compared with surgery group, WS group would increase the risk of local recurrence rate, but WS group had better 2-year DFS and OS than surgery group. However, WS group did not increase the possibility of distant metastasis and cancer related death of the patients.
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