Cervical cancer (CC) is the fourth leading cancer among women and is one of the principal gynecological malignancies. In the tumor microenvironment, cancer-associated fibroblasts (CAFs) play a crucial role during malignant progression, exhibiting a variety of heterogeneous phenotypes. CAFs express phenotypic markers like fibroblast activation protein (FAP), vimentin, S100A4, α-smooth muscle actin (αSMA), and functional markers such as MMP9. This study aimed to evaluate the protein expression of vimentin, S100A4, αSMA, FAP, and MMP9 in mesenchymal stem cells (MSC)-CAF cells, as well as in cervical cancer samples. MSC cells were stimulated with HeLa and SiHa tumor cell supernatants, followed by protein evaluation and cytokine profile to confirm differentiation towards a CAF phenotype. In addition, automated immunohistochemistry (IHQa) was performed to evaluate the expression of these proteins in CC samples at different stages. Our findings revealed a high expression of FAP in stimulated MSC cells, accompanied by the secretion of pro/anti-inflammatory cytokines. In the other hand, CC samples were observed to have high expression of FAP, vimentin, αSMA, and MMP9. Most importantly, there was a high expression of their activation proteins αSMA and FAP during the different stages. In the early stages, a myofibroblast-like phenotype (CAFs αSMA+ FAP+), and in the late stages a protumoral phenotype (CAF αSMA− FAP+). In summary, FAP has a crucial role in the activation of CAFs during cervical cancer progression.

Head and neck squamous cell carcinoma (HNSCC) is a group of cancers originating from the mucosal epithelium in the oral cavity, larynx, oropharynx, nasopharynx, and hypopharynx. Molecular factors can be key in the diagnosis, prognosis, and treatment of HNSCC patients. Long non-coding RNAs (lncRNAs) are molecular regulators composed of 200 to 100,000 nucleotides that act on the modulation of genes that activate signaling pathways associated with oncogenic processes such as proliferation, migration, invasion, and metastasis in tumor cells. However, up until now, few studies have discussed the participation of lncRNAs in modeling the tumor microenvironment (TME) to generate a protumor or antitumor environment. Nevertheless, some immune-related lncRNAs have clinical relevance, since AL139158.2, AL031985.3, AC104794.2, AC099343.3, AL357519.1, SBDSP1, AS1AC108010.1, and TM4SF19-AS1 have been associated with overall survival (OS). MANCR is also related to poor OS and disease-specific survival. MiR31HG, TM4SF19-AS1, and LINC01123 are associated with poor prognosis. Meanwhile, LINC02195 and TRG-AS1 overexpression is associated with favorable prognosis. Moreover, ANRIL lncRNA induces resistance to cisplatin by inhibiting apoptosis. A superior understanding of the molecular mechanisms of lncRNAs that modify the characteristics of TME could contribute to increasing the efficacy of immunotherapy.

MiR-204 is a small noncoding RNA with diverse regulatory roles in breast cancer (BC) development and progression. miR-204 is implicated in the instauration of fundamental traits acquired during the multistep development of BC known as hallmarks of cancer. It may act as a potent tumor suppressor by inhibiting key cellular processes like angiogenesis, vasculogenic mimicry, invasion, migration, and metastasis. It achieves this by targeting multiple master genes involved in these processes, including HIF-1α, β-catenin, VEGFA, FAK, FOXA1, among others. Additionally, miR-204 modulates signaling pathways like PI3K/AKT and interacts with HOTAIR and DSCAM-AS1 lncRNAs, further influencing tumor progression. Beyond its direct effects on tumor cells, miR-204 shapes the tumor microenvironment by regulating immune cell infiltration, suppressing pro-tumorigenic cytokine production, and potentially influencing immunotherapy response. Moreover, miR-204 plays a crucial role in metabolic reprogramming by directly suppressing metabolic genes within tumor cells, indirectly affecting metabolism through exosome signaling, and remodeling metabolic flux within the tumor microenvironment. This review aims to present an update on the current knowledge regarding the role of miR-204 in the hallmarks of BC. In conclusion, miR-204 is a potential therapeutic target and prognostic marker in BC, emphasizing the need for further research to fully elucidate its complex roles in orchestrating aggressive BC behavior.