F. nucleatum is an oral anaerobic opportunistic pathogen considered a risk factor for CRC [3]. A recent study showed that the endogenous retroviral-associated adenocarcinoma lncRNA (EVADR) was specifically upregulated in metastatic CRC tissues infected by F. nucleatum, further conjecturing and confirming that F. nucleatum can promote the translation of Snail, Slug, and ZEB1 mRNAs through the lncRNA EVADR-YBX1 axis, thus inducing EMT [38] (Figure 2). EMT is the process by which epithelial cells transform into a migratory and invasive mesenchymal phenotype [39]. During this transformation, cells develop loose cell–cell connections and become motile, which results in cancer cell metastasis [40]. EMT is triggered by the dysregulation of the core EMT transcription factors (EMT-TFs), Snail, Slug, and ZEB1, which are essential for maintaining normal epithelial structure [41,42]. A protein called YBX1 regulates mRNA transcription and splicing by binding to DNA/RNA, and it can stimulate the translation of EMT-TFs [43,44]. In summary, EVADR directs RNA-binding protein (RBP) YBX1 to recruit its mRNA partners, including Snail, Slug, and ZEB1, to polyribosomes, thereby inducing EMT, ultimately facilitating CRC metastasis. In addition, Chen et al. discovered that F. nucleatum infection promoting CRC metastasis could be achieved by upregulating KRT7-AS/KRT7 [17] (Figure 2). The lncRNAs KRT7-AS have been linked to the proliferation and migration of gastric cancer cells in earlier research, and the current study further verified this connection with the metastasis of CRC [17,45]. A downstream target of KRT7-AS that regulates CRC metastasis is KRT7, a type II cytokeratin that can preserve cellular structural integrity and may also increase motile activity [17,46,47]. F. nucleatum infection activates the NF-κB pathway, a key regulator of immunity and inflammation whose improper regulation is linked to cancer; activated NF-κB P-p65 (activated NF-κB subunit) may upregulate KRT7-AS by increasing the transcriptional activity of KRT7-AS [17,48]. In conclusion, lncRNAs can potentially mediate the role of F. nucleatum in promoting CRC metastasis, and these novel mechanisms by which F. nucleatum promotes CRC metastasis may offer fresh perspectives on how to treat patients with metastatic CRC.In addition, F. nucleatum can also increase CRC glycolysis by targeting lncRNA enolase1-intronic transcript 1 (ENO1-IT1) and KAT7 histone modification axis, and the activation of glycolysis is one of the causes of chemotherapy failure [49,50,51] (Figure 2). The specific mechanism is that F. nucleatum upregulates the binding efficiency of the transcription factor SP1 to the promoter region of lncRNA ENO1-IT1 to activate the transcription of lncRNA ENO1- IT1 and subsequently direct the histone acetyltransferase KAT7 to mediate histone modifications on lncRNA ENO1-IT1 target genes, including ENO1, thereby altering the biological function of CRC, including increasing lactate production, glucose uptake, and cell proliferation that is dependent on glycolysis [49]. KAT7 is a major member of the MYST family of histone acetyltransferases and plays an important role in DNA replication, gene transcription, and embryonic development [52,53,54]. ENO1 can regulate the process related to glycolysis as a key enzyme in the glycolytic pathway [55]. Therefore, targeting ENO1 might improve the sensitivity to chemotherapy and reduce the resistance to oxaliplatin and 5-fluorouracil (5-FU) by inhibiting F. nucleatum-induced glycolysis in CRC patients [49]. Given that the combination of oxaliplatin and 5-FU can inhibit DNA synthesis and transcription, thus leading to apoptosis, it is effective to target ENO1 to treat patients with advanced CRC with high levels of F. nucleatum [49,56,57]. However, it is still important to determine if, in addition to the enhancement of tumor glycolysis, the method by which F. nucleatum upregulates ENO1 to increase drug resistance is connected to other potential processes. Everything considered, F. nucleatum activates glycolysis in CRC via targeting the lncRNA ENO1- IT1, which promotes the development of CRC and chemotherapeutic drug resistance in CRC patients, resulting in a poor prognosis.