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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
microRNA-375 inhibits colorectal cancer cells proliferation by downregulating JAK2/STAT3 and MAP3K8/ERK signaling
Ran Wei1,2, Qin Yang1, Bing Han1,3
1School of Life Science, Yunnan University, Kunming, Yunnan, 650091, P.R. China.
Abstract:
MicroRNA-375 is involved in many types of alimentary system cancers. Our previous studies showed that microRNA-375 was significantly down-regulated in carcinoma tissues compared with para-carcinoma tissues, which strongly indicates that microRNA-375 might suppress the occurrence and development of colorectal cancer. However, the mechanism underlying the microRNA-375 regulation in colorectal cancer remains unclear. In this study, we first sorted out jak2, map3k8 and atg7 as microRNA-375 targeted genes from multiple databases, and found that jak2, map3k8 and their downstream genes stat3 and erk were up-regulated in carcinoma tissues. Secondly, we over-expressed microRNA-375 in colorectal cancer cell lines (HCT116, Caco2 and HT29). Our results showed that in microRNA-375 over-expressing cells, JAK2/STAT3 and MAP3K8/ERK proteins were down-regulated, cell proliferation was inhibited, cell migration rate did not change. There was no significant difference on ATG7 expression between the control group and microRNA-375 over-expressing HT29/Caco2 cells, whereas microRNA-375 down-regulated ATG7 specifically in HCT116 cells. Finally, we demonstrated that expressing microRNA-375 suppressed tumor formation in nude mice. In conclusion, microRNA-375 might function as a tumor-repressive gene to inhibit cell proliferation, mainly through targeting both JAK2/STAT3 and MAP3K8/ERK signaling pathways in colorectal cancer. These findings suggest miR-375 as a promising diagnostic marker and a therapeutic drug for colorectal cancer.
Insights
MicroRNA-375 acts as a tumor suppressor in colorectal cancer by inhibiting cell proliferation through the JAK2/STAT3 and MAP3K8/ERK pathways. This suggests miR-375 as a potential diagnostic marker and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-375 (miR-375) is implicated in various cancers of the digestive system.
- Down-regulation of miR-375 in colorectal cancer (CRC) tissues suggests a tumor-suppressive role.
- The precise mechanisms of miR-375 regulation in CRC are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms by which microRNA-375 influences colorectal cancer progression.
- To identify potential molecular targets of microRNA-375 in colorectal cancer.
- To evaluate the therapeutic potential of microRNA-375 in colorectal cancer models.
Main Methods:
- Bioinformatic analysis to identify potential miR-375 target genes (JAK2, MAP3K8, ATG7).
- Overexpression of miR-375 in CRC cell lines (HCT116, Caco2, HT29) followed by protein expression analysis (JAK2/STAT3, MAP3K8/ERK, ATG7).
- Assessment of cell proliferation and migration, and in vivo tumor formation studies in nude mice.
Main Results:
- JAK2, MAP3K8, and their downstream effectors STAT3 and ERK were upregulated in CRC tissues.
- Overexpression of miR-375 led to decreased JAK2/STAT3 and MAP3K8/ERK signaling and inhibited cell proliferation.
- miR-375 suppressed tumor formation in vivo and differentially affected ATG7 expression in CRC cell lines.
Conclusions:
- MicroRNA-375 functions as a tumor suppressor in colorectal cancer, primarily by targeting the JAK2/STAT3 and MAP3K8/ERK signaling pathways.
- miR-375 inhibits cancer cell proliferation and tumor formation.
- These findings highlight miR-375 as a promising diagnostic biomarker and therapeutic agent for colorectal cancer.
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