Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC...Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway.Here,we found that LSM12 is highly expressed in CRC patient-derived tissues and cells.LSM12 is involved in the proliferation,invasion,and apoptosis of CRC cells,similar to the function of WNT signaling in CRC.Furthermore,protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1(also known asβ-Catenin)and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway.LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis.Taken together,we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation,and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.展开更多
Objective This study aimed to investigate the role of LSM12 in uveal melanoma(UM)oncogenesis and progression,examining its potential as both a prognostic biomarker and therapeutic target.Methods LSM12 expression was a...Objective This study aimed to investigate the role of LSM12 in uveal melanoma(UM)oncogenesis and progression,examining its potential as both a prognostic biomarker and therapeutic target.Methods LSM12 expression was analyzed in relation to RNA modification genes and tumor stemness in UM.UM cell lines were subjected to LSM12 knockdown using siRNA,followed by cell viability and migration assays.The therapeutic potential of targeting LSM12 was evaluated using a subcutaneous xenograft model.Additionally,the relationship between LSM12 and the PI3K/Akt/mTOR pathway was explored.Results LSM12 expression levels were significantly elevated in UM patients,correlating strongly with poor prognosis.Positive correlations were observed between LSM12 expression and multiple genes associated with RNA methylation modifications and cancer stem cell characteristics.Knockdown of LSM12 effectively disrupted UM cell viability and migration in vitro and inhibited OCM1 xenograft growth in vivo.Additionally,LSM12 knockdown resulted in notable inhibition of the PI3K/Akt/mTOR pathway both in vitro and in vivo.Conclusions Elevated LSM12 expression correlates with poor prognosis in UM and critically promotes oncogenic processes,including tumor cell viability,migration,and tumorigenesis.展开更多
基金supported by the Science and Technology Support Plan Key Projects of Tianjin(Grant No.20YFZCSY00070)the National Natural Science Foundation of China(Grant Nos.82073276,82273100)+1 种基金the China Digestive Tumor Clinical Scientific Research Public Welfare Project(Grant No.P014-058)Science and Technology project of Health Commission of Tianjin Binhai New Area(Grant No.2022BWKY016).
文摘Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway.Here,we found that LSM12 is highly expressed in CRC patient-derived tissues and cells.LSM12 is involved in the proliferation,invasion,and apoptosis of CRC cells,similar to the function of WNT signaling in CRC.Furthermore,protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1(also known asβ-Catenin)and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway.LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis.Taken together,we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation,and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.
基金supported by the National Natural Science Foundation of China(Grant Nos.82471068)Research Funds of the State Key Laboratory of Ophthalmology,China(Grant Nos.2025QZLH04).
文摘Objective This study aimed to investigate the role of LSM12 in uveal melanoma(UM)oncogenesis and progression,examining its potential as both a prognostic biomarker and therapeutic target.Methods LSM12 expression was analyzed in relation to RNA modification genes and tumor stemness in UM.UM cell lines were subjected to LSM12 knockdown using siRNA,followed by cell viability and migration assays.The therapeutic potential of targeting LSM12 was evaluated using a subcutaneous xenograft model.Additionally,the relationship between LSM12 and the PI3K/Akt/mTOR pathway was explored.Results LSM12 expression levels were significantly elevated in UM patients,correlating strongly with poor prognosis.Positive correlations were observed between LSM12 expression and multiple genes associated with RNA methylation modifications and cancer stem cell characteristics.Knockdown of LSM12 effectively disrupted UM cell viability and migration in vitro and inhibited OCM1 xenograft growth in vivo.Additionally,LSM12 knockdown resulted in notable inhibition of the PI3K/Akt/mTOR pathway both in vitro and in vivo.Conclusions Elevated LSM12 expression correlates with poor prognosis in UM and critically promotes oncogenic processes,including tumor cell viability,migration,and tumorigenesis.
