Cutaneous T-cell lymphoma is a type of non-Hodgkin lymphoma that belongs to a large group of lymphoproliferative disorders, and is T-cell-derived involving the skin (Willemze et al., 2019). Data derived from the Surveillance, Epidemiology, and End Results (SEER) Program reported an incidence of 8.55 per million cases, and an increasing trend, between 2000 and 2018 in the United States (Cai et al., 2022). The annual incidence has continued to increase over past several decades. When classified by age, race, and gender, CTCL has reported variations. There was an increased incidence in men compared to women with a ratio of 1.9, as well a higher incidence in African Americans (AA) in comparison to other races with a ratio of 1.5 between AA and whites. Additionally, the incidence was higher in older groups with 24.6 per million persons in comparison to the younger groups with an incidence of 0.1 per million persons (Criscione & Weinstock, 2007). CTCL can be stratified based on the 2018 WHO-ERTC classification (Willemze et al., 2005, Willemze et al., 2019). Making up the majority of CTCLS are Mycosis fungoides, Sezary syndrome, and CD301 lymphoproliferative disorder. The remaining CTCLs are subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma, nasal type etc (Willemze et al., 2005).

As the most common type of CTCL, Mycosis fungoides are known to be indolent in nature and present initially as an oval erythematous patch that can disseminate into thick scaly plaque very slowly (Gemmill, 2006, Pulitzer, 2017). They rarely involve lymph nodes, bone marrow, and multiple organs, however, late progression may present in the form of immunosuppression. Often misdiagnosed as inflammatory conditions like psoriasis or eczema, the diagnosis is done with a biopsy (Gemmill, 2006). Sezary syndrome, on the other hand, is a leukemic variant of CTCL that is known to have a poor prognosis. The median survival time is estimated to be 2.5–5 years (Gemmill, 2006). It presents with pruritic erythroderma, lymphadenopathy, and the presence of malignant cells in the skin, lymph nodes, and other organs (Willemze et al., 2019).

Due to its slow progressive nature, mycosis fungoides is treated in its limited stages with empirical methods (Wilcox, 2017). Patients typically undergo observation or skin-related therapies. At a limited stage, a clinical trial was conducted using a combination of radiotherapy and multiple chemotherapeutic agents (Wilcox, 2011). Despite displaying strong success rates, it failed to produce a significant impact on survival. In the early stages, treatment with these agents is considered unnecessary because patients may experience toxicities without significant benefit. However, in the late stages of mycosis fungoides, biologic-response modifiers such as bexarotene and interferon alpha are used (Wilcox, 2011). Bexarotene regulates biological processes as a retinoid, while interferon alpha acts as an immunomodulator (Wilcox, 2011, Wilcox, 2017). Vorinostat, a histone deacetylase inhibitor (HDAC inhibitor) (Kong et al., 2012), targets gene transcription in tumor cells and denileukin diftitox targets the IL-2 receptor, inducing apoptosis. Low doses of methotrexate, cyclophosphamide, and etoposide are used for initial stages or for patients who are poorly responsive, while doxorubicin and gemcitabine have been used for well-tolerated patients (Wilcox, 2017). Other factors such as disease progression and previous therapy are important to consider when choosing an agent, but side effects play a major role in the continuation of treatment, as the response can take months to occur (Wilcox, 2011, Wilcox, 2017).

Non-coding RNAs are RNA molecules that do not translate into a protein (Ahmad et al., 2022, Hadjicharalambous and Lindsay, 2019, Panni et al., 2020). For a long time, these non-coding RNAs were considered cellular junk (Ahmad, 2016). Instead, they have now been found to play a role in processes such as gene regulation, modification, and innate and adaptive immunity (Aird et al., 2018, Hadjicharalambous and Lindsay, 2019, Luginbuhl et al., 2017). Further research has led to the classification of non-coding RNAs into several classes, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), each with its own unique structure, function, and mechanism (Chao et al., 2022, Elkhodiry and El Tayebi, 2021). miRNAs are small molecules with an average nucleotide length of 22 (Hassan et al., 2012, Ling et al., 2013). They regulate protein expression by a process called RNA interference (RNAi) which involves the binding of miRNA to the 3′ untranslated region of the RNA transcript (Mattick & Makunin, 2006). This binding causes degradation of the RNA molecule at the target by a RASC complex. The evolving knowledge on the functionality of miRNAs has contributed a lot in our understanding of the regulation of processes such as cell proliferation, apoptosis, differentiation, among others (Mattick & Makunin, 2006). Any alterations in the target site or sequence can alter the miRNA-mediated regulation, thus playing a role in cancer development (Mattick & Makunin, 2006). LncRNAs, which are characterized by their large size of over 200 nucleotides (Beylerli et al., 2022, Gareev et al., 2021, Panni et al., 2020), are classified into five groups: sense, antisense, bidirectional, intronic, and intergenic. Like short non-coding RNAs, lncRNAs also play a role in gene regulation and have multiple mechanisms for their function, such as binding to regulatory proteins and miRNAs (Bhat et al., 2016, Chen and Shan, 2020, Khan and Ahmad, 2022, Sandberg et al., 2013, Statello et al., 2021).