Macrophages are immune cells that can adopt different functional states within the tumor microenvironment. The review describes a balance between pro-inflammatory M1 macrophages and pro-tumorigenic M2 macrophages. M2 polarization can favor processes associated with tumor progression, whereas M1 polarization is linked in the reviewed evidence to inhibition of tumor growth.

Several non-coding RNAs are linked with M2 polarization in the review. miR-934, lncRNA RPPH1 and circPLCE1 are associated with M2 polarization and metastasis through signaling involving PI3K/AKT, NF-κB and STAT3. Their effects are presented as part of the molecular communication networks that connect colorectal cancer cells with tumor-associated macrophages. The review places these molecules within the broader biological context of tumor progression and metastatic behavior.

Other non-coding RNAs are associated with the M1 state. miR-195-5p and lncRNA GAS5 are described in the reviewed literature as favoring M1 polarization and suppressing tumor growth. The contrast between these molecules illustrates that non-coding RNA activity can be associated with different macrophage states and opposing effects on tumor-related processes. The mechanisms summarized in the review include exosomal transfer, competing endogenous RNA interactions and transcriptional regulation.

Transcriptional regulation provides another level at which these signals can affect cellular behavior. Together, these mechanisms form intricate communication networks between colorectal cancer cells and immune components, including tumor-associated macrophages. The review also discusses the possible translational applications of this biology.

Circulating exosomal non-coding RNAs are presented as candidate biomarkers that could improve diagnostic precision, and ncRNA-regulated macrophage polarization is identified as a possible target for immunomodulatory and precision-treatment strategies. These are research opportunities rather than established clinical benefits. Colorectal cancer remains a major global health burden, with incidence and mortality rates continuing to rise worldwide, according to the review.

The article cites a projection of 3.2 million colorectal cancer cases by 2040 and attributes this expected burden to complex interactions among genetic, environmental and lifestyle factors. The review positions ncRNA signaling within this wider disease context because these molecules may influence tumor-cell behavior, immune evasion, therapeutic resistance and the states of macrophages in the tumor microenvironment. Its central conclusion is that targeting ncRNA-regulated macrophage polarization holds promise for developing next-generation precision therapies and advancing immunomodulatory strategies in colorectal cancer.

That conclusion is a direction for research, not evidence of clinical efficacy. The review’s contribution is to assemble current knowledge about how microRNAs, long non-coding RNAs and circular RNAs relate to macrophage polarization and cancer progression, providing a framework for further investigation of these molecular connections.

Subject of Research: Non-coding RNA regulation of tumor-associated macrophage polarization in colorectal cancer

Article Title: Macrophage polarization and non-coding RNAs in colorectal cancer progression and metastasis

Article References: Nami, M. T., Fattahiyan, I., Eini, P., Eramian, M., & Vanan, A. G. (2026). Macrophage polarization and non-coding RNAs in colorectal cancer progression and metastasis. Medical Oncology, 43(11), Article 350. https://doi.org/10.1007/s12032-026-03482-5

Image Credits: AI Generated

DOI: 10.1007/s12032-026-03482-5

Keywords: colorectal cancer, non-coding RNAs, tumor-associated macrophages, macrophage polarization, microRNAs, long non-coding RNAs, circular RNAs, cancer metastasis, tumor microenvironment, exosomal biomarkers, Macrophage, polarization