scholarly journals Long noncoding RNA XIST suppresses tumorigenesis and enhances radiosensitivity in neuroblastoma cells through regulating miR-653-5p/HK2 axis

2020 ◽  
Author(s):  
Liping Mu ◽  
Lili Wang ◽  
Shaoming Zhang ◽  
Qinghua Wang
Keyword(s):  
Colony Formation ◽  
Noncoding Rna ◽  
Neuroblastoma Cells ◽  
Lactate Production ◽  
Xenograft Model ◽  
Glucose Consumption ◽  
Luciferase Reporter ◽  
Glucose Assay

Abstract Background: Abnormal expression of long noncoding RNAs (lncRNAs) was usually involved in tumorigenesis and radiosensitivity of various cancers. The aim of this study was to explore the biological function and regulatory mechanism of lncRNA X-inactive specific transcript (XIST) in tumorigenesis and radiosensitivity of neuroblastoma (NB).Methods: The expression levels of XIST, microRNA-653-5p (miR-653-5p) and hexokinase 2 (HK2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methylthiazolyldiphenyl tetrazolium bromide (MTT) assay, colony formation assay and transwell assay were utilized to detect cell viability, colony formation and cell invasion abilities. Glucose consumption or lactate production was measured by glucose assay kit or lactate assay kit, respectively. The mice xenograft model was established to investigate the role of XIST in vivo. The interaction between miR-653-5p and XIST or HK2 was predicted by starBase v2.0 and verified by dual-luciferase reporter assay. Western blot was used to measure the protein expression of HK2.Results: XIST and HK2 were highly expressed whilst miR-653-5p was lowly expressed in NB tissues and cells. XIST knockdown inhibited tumorigenesis by repressing NB cell proliferation and invasion. Meanwhile, XIST downregulation increased the radiosensitivity via inhibiting colony formation rates and glycolysis. Moreover, miR-653-5p could bind to XIST and its downregulation reversed the effects of XIST knockdown on tumorigenesis and radiosensitivity. Additionally, HK2 was a direct target of miR-653-5p and its overexpression attenuated the effects of miR-653-5p restoration on suppression of tumorigenesis and promotion of radiosensitivity. Besides, XIST functioned as a molecular sponge of miR-653-5p to regulate HK2 expression. Furthermore, XIST knockdown also suppressed tumor growth by upregulating miR-653-5p and downregulating HK2 in vivo.Conclusion: XIST interference inhibited tumorigenesis and increased radiosensitivity in NB by regulating miR-653-5p/HK2 axis, providing a novel therapeutic strategy for NB.

scholarly journals Long noncoding RNA XIST suppresses tumorigenesis and enhances radiosensitivity in neuroblastoma cells through regulating miR-653-5p/HK2 axis

2020 ◽  
Author(s):  
Liping Mou ◽  
Lili Wang ◽  
Shaoming Zhang ◽  
Qinghua Wang
Keyword(s):  
Colony Formation ◽  
Noncoding Rna ◽  
Neuroblastoma Cells ◽  
Lactate Production ◽  
Xenograft Model ◽  
Glucose Consumption ◽  
Luciferase Reporter ◽  
Glucose Assay

Abstract Background: Abnormal expression of long noncoding RNAs (lncRNAs) was usually involved in tumorigenesis and radiosensitivity of various cancers. The aim of this study was to explore the biological function and regulatory mechanism of lncRNA X-inactive specific transcript (XIST) in tumorigenesis and radiosensitivity of neuroblastoma (NB). Methods: The expression levels of XIST, microRNA-653-5p (miR-653-5p) and hexokinase 2 (HK2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methylthiazolyldiphenyl tetrazolium bromide (MTT) assay, colony formation assay and transwell assay were utilized to detect cell viability, colony formation and cell invasion abilities. Glucose consumption or lactate production was measured by glucose assay kit or lactate assay kit, respectively. The mice xenograft model was established to investigate the role of XIST in vivo . The interaction between miR-653-5p and XIST or HK2 was predicted by starBase v2.0 and verified by dual-luciferase reporter assay. Western blot was used to measure the protein expression of HK2. Results: XIST and HK2 were highly expressed whilst miR-653-5p was lowly expressed in NB tissues and cells. XIST knockdown inhibited tumorigenesis by repressing NB cell proliferation and invasion. Meanwhile, XIST downregulation increased the radiosensitivity via inhibiting colony formation rates and glycolysis. Moreover, miR-653-5p could bind to XIST and its downregulation reversed the effects of XIST knockdown on tumorigenesis and radiosensitivity. Additionally, HK2 was a direct target of miR-653-5p and its overexpression attenuated the effects of miR-653-5p restoration on suppression of tumorigenesis and promotion of radiosensitivity. Besides, XIST functioned as a molecular sponge of miR-653-5p to regulate HK2 expression. Furthermore, XIST knockdown also suppressed tumor growth by upregulating miR-653-5p and downregulating HK2 in vivo . Conclusion: XIST interference inhibited tumorigenesis and increased radiosensitivity in NB by regulating miR-653-5p/HK2 axis, providing a novel therapeutic strategy for NB.

scholarly journals Long noncoding RNA XIST suppresses tumorigenesis and enhances radiosensitivity in neuroblastoma cells through regulating miR-653-5p/HK2 axis

2020 ◽  
Author(s):  
Liping Mou ◽  
Lili Wang ◽  
Shaoming Zhang ◽  
Qinghua Wang
Keyword(s):  
Colony Formation ◽  
Noncoding Rna ◽  
Neuroblastoma Cells ◽  
Lactate Production ◽  
Xenograft Model ◽  
Glucose Consumption ◽  
Luciferase Reporter ◽  
Glucose Assay

Abstract Background Abnormal expression of long noncoding RNAs (lncRNAs) was often involved in tumorigenesis and radiosensitivity of various cancers. The aim of this study was to explore the biological function and regulatory mechanism of lncRNA X-inactive specific transcript (XIST) in tumorigenesis and radiosensitivity of neuroblastoma. Methods The expression of XIST, microRNA-329-3p (miR-653-5p) and hexokinase 2 (HK2) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methylthiazolyldiphenyl tetrazolium bromide (MTT) assay, colony formation assay and transwell assay were utilized to detect cell viability, colony formation and cell invasion abilities. Glucose consumption or lactate production was measured by glucose assay kit or lactate assay kit, respectively. The mice xenograft model was established to investigate the role of XIST in vivo. The interaction between miR-653-5p and XIST or HK2 was predicted by starBase v2.0 and verified by dual-luciferase reporter assay. Western blot was used to measure the protein expression of HK2. Results XIST and HK2 were highly expressed while miR-653-5p was lowly expressed in neuroblastoma tissues and cells. XIST knockdown inhibited tumorigenesis by repressing cell proliferation and invasion, and increased the radiosensitivity via inhibiting colony formation rates and glycolysis. XIST knockdown also suppressed tumor growth in vivo. Moreover, miR-653-5p could bind to XIST and its downregulation reversed the effects of XIST knockdown on tumorigenesis and radiosensitivity. Additionally, HK2 was a direct target of miR-653-5p and its overexpression attenuated the effects of miR-653-5p restoration on suppression of tumorigenesis and promotion of radiosensitivity. Besides, XIST functioned as a molecular sponge of miR-653-5p to regulate HK2 expression. Conclusion XIST interference inhibited tumorigenesis and increased radiosensitivity via regulating miR-653-5p/HK2 axis, providing a novel therapeutic strategy for neuroblastoma.

scholarly journals Long noncoding RNA XIST suppresses tumorigenesis and enhances radiosensitivity in neuroblastoma cells through regulating miR-653-5p/HK2 axis

2020 ◽  
Author(s):  
Liping Mou ◽  
Lili Wang ◽  
Shaoming Zhang ◽  
Qinghua Wang
Keyword(s):  
Colony Formation ◽  
Noncoding Rna ◽  
Neuroblastoma Cells ◽  
Lactate Production ◽  
Xenograft Model ◽  
Glucose Consumption ◽  
Luciferase Reporter ◽  
Glucose Assay ◽  
Rna Immunoprecipitation

Abstract Background: Abnormal expression of long noncoding RNAs (lncRNAs) was usually involved in tumorigenesis and radiosensitivity of various cancers. The aim of this study was to explore the biological function and regulatory mechanism of lncRNA X-inactive specific transcript (XIST) in tumorigenesis and radiosensitivity of neuroblastoma (NB).Methods: The expression levels of XIST, microRNA-653-5p (miR-653-5p) and hexokinase 2 (HK2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methylthiazolyldiphenyl tetrazolium bromide (MTT) assay, colony formation assay and transwell assay were utilized to detect cell viability, colony formation and cell invasion abilities. Glucose consumption or lactate production was measured by glucose assay kit or lactate assay kit, respectively. The mice xenograft model was established to investigate the role of XIST in vivo. The interaction between miR-653-5p and XIST or HK2 was predicted by starBase v2.0 and verified by dual-luciferase reporter, RNA Immunoprecipitation (RIP) and RNA pull-down assays. Western blot was used to measure the protein expression of HK2.Results: XIST and HK2 were highly expressed whilst miR-653-5p was lowly expressed in NB tissues and cells. XIST knockdown inhibited tumorigenesis by repressing NB cell proliferation and invasion. Meanwhile, XIST downregulation increased the radiosensitivity via inhibiting colony formation rates and glycolysis. Moreover, miR-653-5p could bind to XIST and its downregulation reversed the effects of XIST knockdown on tumorigenesis and radiosensitivity. Additionally, HK2 was a direct target of miR-653-5p and its overexpression attenuated the effects of miR-653-5p restoration on suppression of tumorigenesis and promotion of radiosensitivity. Besides, XIST functioned as a molecular sponge of miR-653-5p to regulate HK2 expression. Furthermore, XIST knockdown also suppressed tumor growth by upregulating miR-653-5p and downregulating HK2 in vivo.Conclusion: XIST interference inhibited tumorigenesis and increased radiosensitivity in NB by regulating miR-653-5p/HK2 axis, providing a novel therapeutic strategy for NB.

scholarly journals Silencing circSLAMF6 represses cell glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in gastric cancer under hypoxia

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xinhui Fang ◽  
Yangqiu Bai ◽  
Lida Zhang ◽  
Songze Ding
Keyword(s):  
Gastric Cancer ◽  
Lactate Production ◽  
Xenograft Model ◽  
Glucose Consumption ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Glucose Assay

Abstract Background: Gastric cancer (GC) is a malignant tumor of the digestive tract. Hypoxia plays an important role in the development of cancer, including GC. The present study aimed to investigate the role of circular RNA SLAMF6 (circSLAMF6) in the progression of GC under hypoxia. Methods: The expression of circSLAMF6, microRNA-204-5p (miR-204-5p) and myosin heavy chain 9 (MYH9) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). GC cells were maintained under hypoxia (1% O2) for experiments in vitro. Glucose consumption and lactate production were determined by a Glucose Assay Kit and a Lactate Assay Kit, respectively. Levels of all protein were detected by Western blot. Cell migration and invasion were examined by Transwell assay. The interaction between miR-204-5p and circSLAMF6 or MYH9 was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Murine xenograft model was established to explore the role of circSLAMF6 in vivo. Results: CircSLAMF6 expression was increased in GC cells under hypoxia. Hypoxia promoted glycolysis, migration, and invasion in GC cells, which were reversed by circSLAMF6 knockdown. CircSLAMF6 was validated as a miR-204-5p sponge, and MYH9 was a target of miR-204-5p. Functionally, miR-204-5p inhibitor weakened the inhibition of circSLAMF6 knockdown on GC cell progression under hypoxia. Besides, MYH9 depletion suppressed glycolysis, migration, and invasion in GC cells under hypoxia. Importantly, circSLAMF6 deficiency inhibited tumor growth in vivo by regulating the miR-204-5p/MYH9 axis. Conclusion: CircSLAMF6 was involved in glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in GC cells under hypoxia.

scholarly journals Blocking circ-CNST suppresses malignant behaviors of osteosarcoma cells and inhibits glycolysis through circ-CNST-miR-578-LDHA/PDK1 ceRNA networks

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Rui Hu ◽  
Shan Chen ◽  
Jianxin Yan
Keyword(s):  
Colony Formation ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Pyruvate Dehydrogenase Kinase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Physical Interaction ◽  
U2os Cells

Abstract Background CircRNA CNST (circ-CNST) is a newly identified biomarker for prognosis of osteosarcoma (OS). However, its role in OS progression remains to be well documented. Methods Expression of circ-CNST, microRNA (miR)-578, lactate dehydrogenase A (LDHA), and pyruvate dehydrogenase kinase 1 (PDK1) was detected by quantitative real-time polymerase chain reaction and Western blotting. The physical interaction was confirmed by dual-luciferase reporter assay. Cell behaviors and glycolysis were measured by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay, colony formation assay, flow cytometry, transwell assays, xenograft experiment, and commercial kits. Results Circ-CNST was upregulated in human OS tissues and cells, accompanied with downregulation of miR-578 and upregulation of LDHA and PDK1. There were negative correlations between miR-578 expression and circ-CNST or LDHA/PDK1 in OS tissues. Moreover, high circ-CNST/LDHA/PDK1 or low miR-578 might predict shorter overall survival, advanced TNM stages, and lymph node metastasis. Physically, miR-578 was targeted by circ-CNST, and miR-578 could target LDHA/PDK1. Functionally, blocking circ-CNST and restoring miR-578 enhanced apoptosis rate and suppressed cell proliferation, colony formation, migration, and invasion in 143B and U2OS cells, accompanied with decreased glucose consumption, lactate production, and adenosine triphosphate (ATP)/adenosine diphosphate (ADP) ratio. Furthermore, in vivo growth of U2OS cells was retarded by silencing circ-CNST. Depletion of miR-578 could counteract the suppressive role of circ-CNST deficiency in 143B and U2OS cells, and restoring LDHA or PDK1 partially reversed the role of miR-578 inhibition as well. Conclusion Circ-CNST knockdown could antagonize malignant behaviors and glycolysis of OS cells by regulating miR-578-LDHA/PDK1 axes.

scholarly journals LINC00665 Targets miR-214-3p/MAPK1 Axis to Accelerate Hepatocellular Carcinoma Growth and Warburg Effect

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Hongyu Wan ◽  
Yi Tian ◽  
Juan Zhao ◽  
Xiao Su
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Colony Formation ◽  
Warburg Effect ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Tumor Formation ◽  
Luciferase Reporter

Inhibition of aerobic glycolysis is a hopeful method for cancer treatment. In this study, we aimed to explore LINC00665/miR-214-3p/MAPK1 role in regulating cell viability and aerobic glycolysis in hepatocellular carcinoma (HCC). The expressions of LINC00665 in 50 paired HCC tissues and normal tissues were determined by qRT-PCR. Pearson analysis was applied to evaluate the association between the expression levels of miR-214-3p, LINC00665, and MAPK1 in HCC tissues. The interactions between miR-214-3p and LINC00665 or MAPK1 were determined by luciferase reporter assay and RNA immunoprecipitation. CCK-8 and colony formation assays were used for cell viability evaluation. Lactate production, glucose consumption, and ATP levels were measured to assess Warburg effect. The results showed that LINC00665 was overexpressed in HCC, which positively associated with MAPK1 level and negatively associated with miR-214-3p level in HCC tissues. Overexpression of LINC00665 led to significant enhancements in cell viability and colony formation, whereas this effect was weakened when miR-214-3p was overexpressed or MAPK1 was downregulated. In addition, deletion of LINC00665 expression repressed tumor formation in vivo. Mechanically, LINC00665 increased MAPK1 expression through binding to miR-214-3p. Collectively, this study revealed that LINC00665 accelerated cell growth and Warburg effect through sponging miR-214-3p to increase MAPK1 expression in HCC.

scholarly journals The long noncoding RNA PCAT-1 links the microRNA miR-215 to oncogene CRKL-mediated signaling in hepatocellular carcinoma

2017 ◽  
Vol 292 (43) ◽  
pp. 17939-17949 ◽  
Author(s):  
Yanli Ren ◽  
Jinhua Shang ◽  
Jinliang Li ◽  
Wenjuan Liu ◽  
Zhao Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Noncoding Rna ◽  
Biological Significance ◽  
Xenograft Model ◽  
Adaptor Protein ◽  
Gene Profiling ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene

The long non-coding RNA (lncRNA) PCAT-1 resides in the chromosome 8q24 cancer-risk locus and acts as a vital oncogene during tumorigenesis and progression. However, how PCAT-1 is post-transcriptionally regulated, for example, by small ncRNAs, such as microRNAs (miRNAs) is largely unknown. Here, we report how miRNAs regulate PCAT-1 expression and also investigate the biological significance of this regulation in hepatocellular carcinoma (HCC). We found that miR-215, a P53-inducible miRNA, is a key regulator of PCAT-1 expression in HCC and identified an interaction between miR-215 and PCAT-1 in dual luciferase reporter gene assays. We also found that post-transcriptional silencing of PCAT-1 by miR-215 or PCAT-1 siRNAs significantly inhibited proliferation of HCC cells and, conversely, that inhibition of endogenous miR-215 up-regulated PCAT-1 expression and promoted cell viability. The tumor-suppressing role of miR-215 was further confirmed in an in vivo mouse HCC xenograft model. Of note, gene profiling assays suggested that the kinase CRK-like proto-oncogene, adaptor protein (CRKL), is a potential downstream target of the miR–215–PCAT-1 axis in HCC, and we demonstrated that CRKL silencing significantly suppresses cell proliferation. Taken together and considering the essential role of CRKL in cancer cells, we propose that the TP53–miR-215–PCAT-1–CRKL axis might represent an important regulatory pathway in HCC. In summary, our results highlight the involvement of several ncRNAs in HCC and thus provide critical insights into the molecular pathways operating in this malignancy.

scholarly journals Circ_0084043 promotes cell proliferation and glycolysis but blocks cell apoptosis in melanoma via circ_0084043-miR-31-KLF3 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 774-786
Author(s):  
Songjiang Wu ◽  
Yuhan Tang ◽  
Wenli Liu
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Glucose Transporter 1

AbstractMelanoma is an aggressive malignant tumor. The crucial role of circular RNAs has been documented in many types of cancer, including melanoma. The objective of this study was to uncover the function of circ_0084043 in the biological process of melanoma and associated mechanism of action. The expression of circ_0084043, miR-31, and Krüppel-like factor 3 (KLF3) was determined by qRT-PCR. Cell proliferation and apoptosis were monitored by the MTT assay and flow cytometry assay, respectively. The progression of glycolysis was evaluated according to the levels of glucose consumption, lactate production, and ATP concentration using appropriate detection kits. The relationship between miR-31 and circ_0084043 or KLF3 was predicted by the bioinformatics tool and ascertained by the dual-luciferase reporter assay. The protein levels of KLF3 and glucose transporter 1 (Glut1) were quantified by western blot. A xenograft model was established to ascertain the role of circ_0084043 in vivo. As a result, circ_0084043 expression was reinforced in melanoma tissues and cells. Circ_0084043 knockdown inhibited cell proliferation, induced cell apoptosis, and restrained glycolysis. MiR-31 was a target of circ_0084043, and miR-31 deficiency reversed the role of circ_0084043 knockdown. KLF3 was targeted by miR-31, and KLF3 upregulation abolished the effects of miR-31 enrichment. Moreover, circ_0084043 knockdown impeded tumor growth in vivo and suppressed the level of Glut1 by modulating miR-31 and KLF3. Circ_0084043 promoted cell proliferation and glycolysis, and blocked apoptosis through the circ_0084043–miR-31–KLF3 regulatory axis in melanoma.

scholarly journals circ_0005962 functions as an oncogene to aggravate NSCLC progression

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 997-1009
Author(s):  
Zhihong Zhang ◽  
Zhenxiu Shan ◽  
Rubin Chen ◽  
Xiaorong Peng ◽  
Bin Xu ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Lactate Production ◽  
Xenograft Model ◽  
Glucose Consumption ◽  
Pyruvate Dehydrogenase Kinase ◽  
Nuclear Antigen ◽  
Circular Rnas ◽  
Incidence And Mortality

Abstract Background Non-small cell lung cancer (NSCLC) is a leading threat to human lives with high incidence and mortality. Circular RNAs were reported to play important roles in human cancers. The purpose of this study was to investigate the role of circ_0005962 and explore the underlying functional mechanisms. Methods The protein levels of Beclin 1, light chain3 (LC3-II/LC3-I), Pyruvate dehydrogenase kinase 4 (PDK4), Cleaved Caspase 3 (C-caspase 3), and proliferating cell nuclear antigen were examined using western blot analysis. Glycolysis was determined according to the levels of glucose consumption and lactate production. Xenograft model was constructed to investigate the role of circ_0005962 in vivo. Result circ_0005962 expressed with a high level in NSCLC tissues and cells. circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but promoted apoptosis in NSCLC cells. miR-382-5p was targeted by circ_0005962, and its inhibition reversed the role of circ_0005962 knockdown. Besides, PDK4, a target of miR-382-5p, was regulated by circ_0005962 through miR-382-5p, and its overexpression abolished the effects of miR-382-5p reintroduction. circ_0005962 knockdown suppressed tumor growth in vivo. Conclusion circ_0005962 knockdown restrained cell proliferation, autophagy, and glycolysis but stimulated apoptosis through modulating the circ_0005962/miR-382-5p/PDK4 axis. Our study broadened the insights into understanding the mechanism of NSCLC progression.

scholarly journals Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zizhen Si ◽  
Lei Yu ◽  
Haoyu Jing ◽  
Lun Wu ◽  
Xidi Wang
Keyword(s):  
Colorectal Cancer ◽  
Rna Binding ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Cancer Proliferation ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Abstract Background Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. Methods ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. Results We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. Conclusion In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC.

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