PCDH10 exerts tumor-suppressor functions through modulation of EGFR/AKT axis in colorectal cancer

Jao, Tzu-Ming; Fang, Wen‐Hsien; Ciou, Shih‐Ci; Yu, Shan‐Fu; Hung, Yu-Lin; Weng, Wei-Ting; Lin, Tsai-Yi; Tsai, Ming‐Hong; Yang, Ya-Chien

doi:10.1016/j.canlet.2020.11.017

Cited by 22 publications

(17 citation statements)

References 38 publications

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“…TWIST1 is a basic helix-loop-helix transcription factor encoded by the TWIST1 gene. It has proved that this factor is directly related to the pathogenesis of various diseases, like neurocognitive defects [ 22 ], intervertebral discs degeneration [ 23 ], osteoarthritis [ 24 ] and cancer [ 25 , 26 ]. Importantly, TWIST1 is usually seemed as a transcription factor of cancer EMT, playing an essential role in cancer metastasis [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA CNOT2 knockdown regulates twist family BHLH transcription factor via targeting microRNA 409-3p to prevent breast cancer invasion, migration and epithelial–mesenchymal transition

Shen

et al. 2021

Bioengineered

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Numerous studies have manifested that cicular RNA (circRNA) is closely associated with the development of breast cancer (BC), but the specific mechanism has not been fully clarified. The purpose of this study was to investigate the effect of circCNOT2 on BC invasion, migration and epithelial mesenchymal transition (EMT) and its potential molecular mechanism. The results assured that circCNOT2 and Twist Family BHLH Transcription Factor (TWIST1) were elevated in BC, while microrNA (miR)-409-3p was reduced. CircCNOT2 was positively correlated with TWIST1 and negatively correlated with miR-409-3p. Elevated circCNOT2 is associated with poor prognosis of BC. Knockdown circCNOT2 or augmented miR-409-3p could promote apoptosis but repress proliferation, invasion, migration and EMT of BC cells. In addition, overexpression of circCNOT2 or TWIST1 accelerated BC invasion, migration and EMT, which could be reversed by simultaneous transfection of miR-409-3p-mimic. Further dual luciferase reporting and RNA-pull down assay clarified that circCNOT2 acted as a competing endogenous RNA of miR-409-3p to mediate TWIST1 expression. In conclusion, the results of this study suggest that circCNOT2 affects the biological behavior of BC via regulating the miR-409-3p/TWIST1 axis, and may be applied as a potential therapeutic target for BC later.

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Section: Discussionmentioning

confidence: 99%

Circular RNA CNOT2 knockdown regulates twist family BHLH transcription factor via targeting microRNA 409-3p to prevent breast cancer invasion, migration and epithelial–mesenchymal transition

Shen

et al. 2021

Bioengineered

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“… 21 , 23 , 40 A recent research revealed that PCDH10 directly participated in the negative regulation of the EGFR/AKT/β‐catenin signalling pathway, therefore inhibiting the EMT and stemness of CRC cells. 22 However, the upstream regulation of PCDH10 remains indefinite. In our study, we determined that hsa_circ_0001666 suppressed the proliferation, invasion, metastasis and induced apoptosis, as well as inhibited the EMT and stemness through targeting PCDH10 in CRC cells.…”

Section: Discussionmentioning

confidence: 99%

“…Hsa_circ_0001666 suppresses EMT and cell stemness by miR-576-5p/PCDH10 axis in vitro PCDH10 has been reported to be a negative regulator to suppress EMT and cell stemness. 22 Given these results, we wondered whether hsa_circ_0001666 could inhibit EMT and stemness by miR-576-5p/PCDH10 axis. We co-transferred si-hsa_circ_0001666-1/oe-PCDH10 or si-hsa_circ_0001666-1/ PCDH10 Vector and oe-hsa_circ_0001666/si-PCDH10 or oe-hsa_circ_0001666/ PCDH10 NC into LoVo and DLD-1 cell lines, respectively.…”

Section: 8mentioning

confidence: 99%

“…[17][18][19] Functional studies revealed that PCDH10 could inhibit cell proliferation, migration, as well as induce tumour cells apoptosis. 20,21 Moreover, PCDH10 could suppress epithelial-mesenchymal transition (EMT) and stemness in CRC by negatively regulating the EGFR/AKT/β-catenin signalling pathway 22 and defer the development of endometrial endometrioid carcinoma through the PCDH10-Wnt/β-catenin-MALAT1 regulatory axis. 23 Here, we identified a CRC-related circRNA, hsa_circ_ 0001666, as a suppressor of CRC progression.…”

Section: Introductionmentioning

confidence: 99%

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Hsa_circ_0001666 suppresses the progression of colorectal cancer through the miR‐576‐5p/PCDH10 axis

Zhou

Wang

Sun

et al. 2021

Clinical & Translational Med

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BackgroundThough circular RNAs, new non‐coding RNA classes have demonstrated that they have an essential role in the initiation as well as development of CRC (colorectal cancer), whereas in CRC the function and mechanism of hsa_circ_0001666 are less known.MethodsHsa_circ_0001666 was identified by bioinformatics analysis of a circRNA microarray from the GEO database, and its expression in both CRC cell lines and tissues was analysed. A series of in vitro along with in vivo experiments were carried out for exploring the hsa_circ_0001666 functions, including transwell, wound healing, flow cytometry, colony formation, Edu, CCK‐8, soft agar colony formation, tumor xenografts and lung/liver metastasis in mice. RNA pull‐down, RIP (RNA immunoprecipitation), luciferase reporter assay, FISH (fluorescence in situ hybridization) and rescue experiments were used for determining the correlation among hsa_circ_0001666, miR‐576‐5p and PCDH10.ResultsHsa_circ_0001666 was downregulated in both CRC cell lines along with tumour tissues. A higher expression level of hsa_circ_0001666 indicated a better clinical prognosis in patients with CRC. Hsa_circ_0001666 knockdown significantly supported CRC cell proliferation along with invasion and inhibited cell apoptosis in vitro. Hsa_circ_0001666 knockdown accelerated the CRC growth and metastasis in vivo. Moreover, the mechanistic study showed that hsa_circ_0001666, acting as ‘ceRNA’ of miR‐576‐5p, prevented PCDH10 downregulation, as well as suppressed EMT and stemness of CRC cells, and the Wnt/β‐catenin signalling pathway. Inhibiting miR‐576‐5p or overexpressing PCDH10 could reverse phenotypic changes caused by knocking down of hsa_circ_0001666.ConclusionsHsa_circ_0001666 suppresses CRC progression through the miR‐576‐5p/PCDH10 axis and may provide a new insight for the diagnosis and treatment of CRC.

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“…Studies have shown that PCDHs are mainly expressed in the nervous system ( Wang et al, 2002 ), and previous studies have shown that PCDH19 can be regulated by TBR2 and further affect the expansion of mammalian cortical coordinated neurogenesis and the precise assembly of microcircuits ( Lv et al, 2019 ). In the field of cancer, Gao et al found that PCDH10 can directly participate in the negative regulation of the EGFR/Akt/β-Catenin signaling pathway, thereby inhibiting the occurrence and development of colorectal cancer ( Jao et al, 2021 ). In conclusion, limited studies imply that the potential regulatory mechanisms of PCDHs in different physiological and pathological processes need to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Wang

Ding

Cui

et al. 2021

Front. Cell Dev. Biol.

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Fanconi anemia (FA) pathway is a typical and multienzyme-regulated DNA damage repairer that influences the occurrence and development of disease including cancers. Few comprehensive analyses were reported about the role of FA-related genes (FARGs) and their prognostic values in cancers. In this study, a comprehensive pan-cancer analysis on 79 FARGs was performed. According to the correlation analyses between HPV integration sites and FARGs, we found that FARGs played specific and critical roles in HPV-related cancers, especially in cervical cancer (CC). Based on this, a FARGs-associated prognostic risk score (FPS) model was constructed, and subsequently a nomogram model containing the FPS was developed with a good accuracy for CC overall survival (OS) and recurrence-free survival (RFS) outcome prediction. We also used the similar expression pattern of FARGs by consensus clustering analysis to separate the patients into three subgroups that exhibited significant differential OS but not RFS. Moreover, differential expressed genes (DEGs) between the two risk groups or three clusters were identified and immune pathways as well as cell adhesion processes were determined by functional enrichment analysis. Results indicated that FARGs might promote occurrence and development of CC by regulating the immune cells’ infiltration and cell adhesion. In addition, through the machine learning models containing decision tree, random forest, naïve bayes, and support vector machine models, screening of important variables on CC prognosis, we finally determined that ZBTB32 and CENPS were the main elements affecting CC OS, while PALB2 and BRCA2 were for RFS. Kaplan-Meier analysis revealed that bivariate prediction of CC outcome was reliable. Our study systematically analyzed the prognostic prediction values of FARGs and demonstrated their potential mechanism in CC aggressiveness. Results provided perspective in FA pathway-associated modification and theoretical basis for CC clinical treatments.

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PCDH10 exerts tumor-suppressor functions through modulation of EGFR/AKT axis in colorectal cancer

Cited by 22 publications

References 38 publications

Circular RNA CNOT2 knockdown regulates twist family BHLH transcription factor via targeting microRNA 409-3p to prevent breast cancer invasion, migration and epithelial–mesenchymal transition

Circular RNA CNOT2 knockdown regulates twist family BHLH transcription factor via targeting microRNA 409-3p to prevent breast cancer invasion, migration and epithelial–mesenchymal transition

Hsa_circ_0001666 suppresses the progression of colorectal cancer through the miR‐576‐5p/PCDH10 axis

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

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