Molecular interplay of pro-inflammatory transcription factors and non-coding RNAs in esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma is the sixth most common cancer in the developing world. The aggressive nature of esophageal squamous cell carcinoma, its tendency for relapse, and the poor survival prospects of patients diagnosed at advanced stages, represent a pressing need for the development of new therapies for this disease. Chronic inflammation is known to have a causal link to cancer pre-disposition. Nuclear factor kappa B and signal transducer and activator of transcription 3 are transcription factors which regulate immunity and inflammation and are emerging as key regulators of tumor initiation, progression, and metastasis. Although these pro-inflammatory factors in esophageal squamous cell carcinoma have been well-characterized with reference to protein-coding targets, their functional interactions with noncoding RNAs have only recently been gaining attention. Non-coding RNAs, especially microRNAs and long non-coding RNAs demonstrate potential as biomarkers and alternative therapeutic targets. In this review, we summarize the recent literature and concepts on non-coding RNAs that are regulated by/regulate nuclear factor kappa B and signal transducer and activator of transcription 3 in esophageal cancer progression. We also discuss how these recent discoveries can pave way for future therapeutic options to treat esophageal squamous cell carcinoma.

Role of the NFκB-signaling pathway in cancer

“…NFκB has hundreds of validated transcriptional targets, 61 and thus NFκB-signaling activity is under stringent spatial and temporal control at the levels of nuclear translocation and posttranslational modifications (PTMs) of signaling components. 61 , 62 There is a wide range of PTMs of NFκB subunits, 63 and PTMs provide essential mechanisms differentially to regulate NFκB-signaling activity in response to the various stimuli that activate this pathway in many cancer cells. 64 , 65 Although these modifications have a critical role in the normal and pathological functions of NFκB in vivo, the physiological significance of PTMs remains unclear in cancer cells.…”

Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma

“…To understand the role of ncRNAs in ESCC progression, numerous investigations on ncRNAs (mainly miRNAs and lncRNAs) in ESCC have been reported [7,8,[29][30][31]. Many studies on the regulation of circRNAs in ESCC are in their early stages.…”

“…Recently, non-coding RNAs (ncRNAs) have gained attention as a potential tool for treating different cancers, including ESCC [7,8]. Conventional transcriptome studies focus on protein-coding genes.…”

Long Noncoding RNAs and Human Osteosarcoma

“…Non coding RNAs (ncRNAs) are endogenously RNA molecules with no capability of coding protein. According to size of nucleotides, ncRNAs can be classified as small non coding RNAs (sncRNAs, <200 nt) and lncRNAs (>200 nt) [13]. The small ncRNA such as microRNAs (miRNAs), transfer RNAs, small interfering RNAs (siRNAs), some ribosomal RNA and piwi-interacting RNAs, have been investigated to function in the tumorigenesis, metastasis and chemo-resistance.…”

“…LncRNAs are considered to have equivalent chromatin signatures to the coding genes. More and more recent researches have pointed out differences in the existence of specific histone letters [14][15][16] and splicing capability [15,17] among lncRNAs and coding genes, as well as with other lncRNAs according to chromatin structure [13,18].…”