lncRNA DCST1-AS1 Facilitates Oral Squamous Cell Carcinoma by Promoting M2 Macrophage Polarization through Activating NF-κB Signaling

Abstract

lncRNAs are related to the progression of various diseases, including oral squamous cell carcinoma (OSCC), which is a common squamous cell carcinoma of the head and neck. Tumor-associated macrophages and tumor cells are significant components of tumor microenvironment. M2 polarization of tumor-associated macrophages is a crucial actor in tumor malignancy and metastasis. In this study, we studied the molecular mechanism of lncRNA DCST1-AS1 in OSCC. Here, we reported that DCST1-AS1 was significantly increased in OSCC cells. We found that loss of DCST1-AS1 obviously inhibited the proliferation, migration, and invasion of OSCC cells and xenograft tumor growth. Meanwhile, silencing of DCST1-AS1 also repressed the percentage of macrophages expressing M2 markers CD206 and CD11b. DCST1-AS1 shRNA enhanced the percentage of macrophages expressing M1 markers CD80 and CD11c. Then, we observed that loss of DCST1-AS1 suppressed OSCC progression via inactivating NF-κB signaling. As well established, NF-κB signaling exerts critical roles in tumor progression, and our study proved that DCST1-AS1 could regulate NF-κB signaling. We proved that blocking the NF-κB pathway using antagonists greatly downregulated OSCC progression and M2 macrophage polarization induced by the overexpression of DCST1-AS1. To sum up, we reported that DCST1-AS1 plays an important role in modulating OSCC tumorigenicity and M2 macrophage polarization through regulating the NF-κB pathway.

A TRP Family Based Signature for Prognosis Prediction in Head and Neck Squamous Cell Carcinoma

“…It worth noting that another group of people has pointed out that a unique population of Tregs might exert tissue-specific roles and suppression effects in visceral adipose tissue, distinguishing from their counterparts in lymph nodes [ 44 – 46 ]. Likewise, M2 macrophages play a central part in tumor progression and metastasis [ 47 , 48 ]. Regarding HNSCC, Saloura et al have once tested Treg markers and M2 macrophages markers expression in HNSCC specimens and normal controls and found that these targets were notably upregulated in HNSCC [ 49 ].…”

The role of long non-coding RNAs in the pathogenesis of head and neck squamous cell carcinoma

“… 60 Another group of researchers has found that lncRNA DCST1-AS1 can activate the NF-κB pathway to promote M2 macrophage polarization, thus advancing OSCC cancer progression. 90 Li et al. have observed that silencing of lncRNA LINC02195 can decrease the MHC I protein expression.…”

The role of tumor-associated macrophages in oral squamous cell carcinoma

“…Tumor cells can secrete CSF-1, which binds to the CSF-1R receptor on the surface of TAMs to promote their polarization to M2 TAMs. The simultaneous activation of hypoxia-inducible factor-1 (HIF-1) and hypoxia-inducible factor-2 (HIF-2) in the TME and NF-Kβ signaling pathway can also lead to the M2 polarization of macrophages ( Dan et al, 2020 ; Ai et al, 2021 ). M2 TAMs promote tumor growth, metastasis, and angiogenesis, while also enhancing tumor immune escape ( Mori et al, 2011 ).…”