Expression alternation and function of small non-coding RNAs in esophagus cancer

۱. Background Small non-coding RNAs (sncRNAs) are essential regulators of various cellular processes including transcription, post-transcriptional modification, and translation. Recent studies have highlighted their significant involvement in cancer progression and their potential utility as biomarkers and therapeutic targets. Dysregulation of sncRNAs has been associated with the development and progression of multiple cancers, including esophageal cancer (EC), which is one of the most lethal malignancies worldwide. Despite advancements in treatment, patient outcomes remain poor owing to an incomplete understanding of the molecular mechanisms driving EC, underscoring the need for novel diagnostic and therapeutic strategies. ۲. Objective This review aims to summarize current knowledge on the expression alterations and functions of sncRNAs in esophageal cancer, focusing on their potential roles in diagnosis, prognosis, and targeted therapy. ۳. Methods A comprehensive literature review was conducted to analyze studies that investigated the expression patterns and biological functions of sncRNAs in esophageal cancer. Relevant databases were searched for recent advancements, with a particular focus on how sncRNAs contribute to tumor initiation, progression, and therapeutic resistance. ۴. Results sncRNAs encompass various families, each with distinct roles in esophageal cancer. Among them, microRNAs (miRNAs) are the most studied ones. Dysregulated miRNAs, such as miR-۲۱, miR-۱۹۲, miR-۱۰۶b, and miR-۳۷۵, have been implicated in tumor growth, metastasis, and poor prognosis in both esophageal adenocarcinoma (ESAD) and esophageal squamous cell carcinoma (ESCC). miR-۲۱, in particular, promotes aggressive tumor behavior, whereas miR-۳۷۵ downregulation accelerates cancer progression. Moreover, miRNAs are critical in modulating the response to radiotherapy. For example, miR-۱۹۳a-۳p induces radioresistance by reducing PSEN۱ expression, whereas miR-۳۰۱a and miR-۳۳۸-۵p enhance radiosensitivity by targeting the Wnt/β-catenin and survivin pathways. Additionally, piwi-interacting RNAs (piRNAs) and their associated PIWI proteins, such as HIWI, have been linked to higher tumor grade, advanced clinical stage, and poor prognosis in ESCC, indicating their potential as biomarkers and therapeutic targets. Small interfering RNAs (siRNAs) offer a promising therapeutic approach by silencing oncogenes, reducing tumor growth and metastasis, and overcoming drug resistance in EC. Small nucleolar RNAs (snoRNAs), such as SNORA۴۲ and SNORD۱۲B, are frequently upregulated in ESCC and promote cancer progression through pathways such as the DHX۹/p۶۵ axis and the AKT-mTOR pathway, respectively, making them potential therapeutic targets. Finally, small nuclear RNAs (snRNAs) such as RNU۶-۱۰۱ P have been identified as risk factors for ESAD and their differential expression correlates with poor survival outcomes. ۵. Conclusion Dysregulation of sncRNAs plays a crucial role in the pathogenesis of esophageal cancer, offering new avenues for biomarker-based diagnostics and targeted therapies. Future research should aim to translate these findings into clinical application to improve patient outcomes.

کلیدواژه ها:

Esophageal cancer (EC) ، Small non-coding RNAs (sncRNAs) ، MicroRNAs (miRNAs) ، Biomarkers ، Radiotherapy resistance