Abstract
microRNAs are aberrantly expressed during the development and progression of a variety of human cancers, including colorectal cancer (CRC). Of these microRNAs, microRNA-375 (miR-375) was previously observed to be downregulated in human colorectal cancer(CRC) plasma and tissues, but its functions are largely unknown. Here, we investigated the impact of miR-375 on CRC metastasis. Specifically, miR-375 expression was significantly decreased in human CRC tissues compared with their matched noncancerous tissues (NCTs), and low levels of miR-375 predicted tumor metastatic potential. The up-regulation of miR-375 suppressed colorectal cancer cell migration and invasion in vitro and reduced tumor metastases in murine models established by both orthotopic implantation and spleen injection. Furthermore, we identified Frizzled 8 (FZD8) as a direct target of miR-375 in CRC, and miR-375 negatively regulated Wnt/β-catenin signaling by suppressing FZD8. More importantly, FZD8 expression inversely correlated with overall survival in human CRC patients and is a likely independent predictor of survival. Therefore, we concluded that miR-375 functions as a tumor-suppressive microRNA by directly acting upon FZD8, which may serve as a new therapeutic target to inhibit tumor metastasis in CRC.
Highlights
Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of cancer-related death worldwide [1]
We examined the miR-375 levels in all 90 pairs of human colorectal cancer tissues and their corresponding noncancerous tissues (NCTs) by quantitative reverse transcription polymerase chain reaction (qRT-PCR)
Because vessel emboli have been associated with an increased incidence of tumor metastasis and an overall decrease in the survival rate [19,20], we investigated the relationship between low miR375 expression and colorectal cancer (CRC) metastasis
Summary
Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of cancer-related death worldwide [1]. Deregulated miRNAs have been found to be associated with tumor initiation, promotion and progression by acting on many oncogenes and tumor suppressors They have been correlated with disease stage, metastasis and survival in numerous human cancers, including CRC [11]. Some miRNAs that act as tumor suppressors are downregulated in tumorigenesis, whereas other miRNAs are over-expressed in cancer tissue www.impactjournals.com/oncotarget compared with normal tissues and act as tumor promoters [12, 13]. Among these miRNAs, miR-375 has recently been documented to be downregulated in various types of cancers. The contribution of this down-regulation to the development and progression of CRC remains unknown, and the related mechanisms and functions of miR-375 in CRC are yet to be determined
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
