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MEIS2 suppresses breast cancer development by downregulating IL10
Yongzhi Xiao1, Yingzhe Liu2, Yangqing Sun3
1Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Background:
Breast cancer (BC) is the most commonly diagnosed female cancer. Homeobox protein MEIS2, a key transcription factor, is involved in the regulation of many developmental and cellular processes. However, the role of MEIS2 in the development of breast cancer is still unclear.
Aims:
We aimed to examine the role of myeloid ecotropic insertion site (MEIS2) in breast cancer and the association of MEIS2 with breast cancer clinical stages and pathological grades. We revealed the underlying mechanism by which MEIS2 affected breast cancer cell growth and tumor development.
Methods And Results:
Using human BC cell lines, clinical samples and animal xenograft model, we reveal that MEIS2 functions as a tumor suppressor in breast cancer. The expression of MEIS2 is inversely correlated with BC clinical stages and pathological grades. MEIS2 knockdown (MEIS2-KD) promotes while MEIS2 overexpression suppresses breast cancer cell proliferation and tumor development in vitro and in animal xenograft models, respectively. To determine the biological function of MEIS2, we screen the expression of a group of MEIS2 potential targeting genes in stable-established cell lines. Results show that the knockdown of MEIS2 in breast cancer cells up-regulates the IL10 expression, but MEIS2 overexpression opposed the effect on IL10 expression. Furthermore, the suppressive role of MEIS2 in breast cancer cell proliferation is associated with the IL10 expression and myeloid cells infiltration.
Conclusion:
Our study demonstrates that the tumor suppressor of MEIS2 in breast cancer progression is partially via down regulating the expression of IL10 and promoting myeloid cells infiltration. Targeting MEIS2 would be a potentially therapeutic avenue for BC.
Insights
Homeobox protein MEIS2 acts as a tumor suppressor in breast cancer. Lower MEIS2 levels correlate with advanced stages, while targeting MEIS2 may offer new breast cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Breast cancer (BC) is a leading female cancer.
- Homeobox protein MEIS2 regulates cellular processes, but its role in BC is unknown.
Purpose of the Study:
- Investigate MEIS2's role in breast cancer.
- Determine MEIS2's association with BC stages and grades.
- Elucidate MEIS2's mechanism in BC cell growth and tumor development.
Main Methods:
- Analysis of human BC cell lines, clinical samples, and xenograft models.
- MEIS2 knockdown and overexpression experiments.
- Screening of MEIS2 target genes, including IL10.
- Assessment of myeloid cell infiltration.
Main Results:
- MEIS2 functions as a tumor suppressor in breast cancer.
- MEIS2 expression inversely correlates with BC stage and grade.
- MEIS2 knockdown increases IL10 expression and proliferation; MEIS2 overexpression suppresses them.
- MEIS2's suppressive role involves IL10 regulation and myeloid cell infiltration.
Conclusions:
- MEIS2 suppresses breast cancer progression by downregulating IL10 and promoting myeloid cell infiltration.
- Targeting MEIS2 presents a potential therapeutic strategy for breast cancer.
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