Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (mi...Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (miRNAs) are evolutionarily conserved molecules that modulate the expression of their target genes post-transcriptionally, and they may participate in various physiological and pathological processes including CRC metastasis by influencing various factors in the human body. Recently, the role miRNAs play throughout the CRC metastatic cascade has gain attention. Many studies have been published to link them with CRC metastasis. In this review, we will briefly discuss metastatic steps in the light of miRNAs, along with their target genes. We will discuss how the aberration in the expression of miRNAs leads to the formation of CRC by effecting the regulation of their target genes. As miRNAs are being exploited for diagnosis, prognosis, and monitoring of cancer and other diseases, their high tissue specificity and critical role in oncogenesis make them new biomarkers for the diagnosis and classification of cancer as well as for predicting patients’ outcome. MiRNA signatures have been identified for many human tumors including CRC, and miRNA-based therapies to treat cancer have been emphasized lately. These will also be discussed in this review.展开更多
P21-activated kinase 1(PAK1)plays an oncogenic role in colorectal cancer(CRC).However,the role of PAK1 in CRC progression remains incompletely understood.Here,we showed that PAK1 enhanced the mRNA stability of multipl...P21-activated kinase 1(PAK1)plays an oncogenic role in colorectal cancer(CRC).However,the role of PAK1 in CRC progression remains incompletely understood.Here,we showed that PAK1 enhanced the mRNA stability of multiple oncogenic factors.We found that PAK1 promoted CRC initiation and progression as previously reported.Mechanistically,loss of PAK1 promoted mRNA decay and inhibited the expression of CD44,SAA1,MTOR,RPS6KB1,and EIF4G1,the factors involved in tumorigenesis in many cancers.Importantly,our results revealed that the PAK1 inhibitor,PF3758309,exhibited a profound synergistic effect with oxaliplatin in CRC.Collectively,our study unveils a novel function of PAK1 in CRC progression.Thus,these results highlight the potential of targeting PAK1 as a therapeutic strategy in CRC,particularly in combination with oxaliplatin.展开更多
文摘Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (miRNAs) are evolutionarily conserved molecules that modulate the expression of their target genes post-transcriptionally, and they may participate in various physiological and pathological processes including CRC metastasis by influencing various factors in the human body. Recently, the role miRNAs play throughout the CRC metastatic cascade has gain attention. Many studies have been published to link them with CRC metastasis. In this review, we will briefly discuss metastatic steps in the light of miRNAs, along with their target genes. We will discuss how the aberration in the expression of miRNAs leads to the formation of CRC by effecting the regulation of their target genes. As miRNAs are being exploited for diagnosis, prognosis, and monitoring of cancer and other diseases, their high tissue specificity and critical role in oncogenesis make them new biomarkers for the diagnosis and classification of cancer as well as for predicting patients’ outcome. MiRNA signatures have been identified for many human tumors including CRC, and miRNA-based therapies to treat cancer have been emphasized lately. These will also be discussed in this review.
基金supported by grants from the National Natural Science Foundation of China(Nos.81902489 and 82172872)the Yishan Research Project of Jiangsu Cancer Hospital(No.YSZD/PY202408)+1 种基金the Key Research and Development Program of Jiangsu Province(BE2021745)the Natural Science Foundation of Jiangsu Province(BK20191079)。
文摘P21-activated kinase 1(PAK1)plays an oncogenic role in colorectal cancer(CRC).However,the role of PAK1 in CRC progression remains incompletely understood.Here,we showed that PAK1 enhanced the mRNA stability of multiple oncogenic factors.We found that PAK1 promoted CRC initiation and progression as previously reported.Mechanistically,loss of PAK1 promoted mRNA decay and inhibited the expression of CD44,SAA1,MTOR,RPS6KB1,and EIF4G1,the factors involved in tumorigenesis in many cancers.Importantly,our results revealed that the PAK1 inhibitor,PF3758309,exhibited a profound synergistic effect with oxaliplatin in CRC.Collectively,our study unveils a novel function of PAK1 in CRC progression.Thus,these results highlight the potential of targeting PAK1 as a therapeutic strategy in CRC,particularly in combination with oxaliplatin.
