Table 2.

COVID-19-associated miRNAs involved in immune response

MicroRNAs	Functions	Types of malignancy	Ref
miRNA-181a and -b	• Regulation of differentiation and development of immune cells and involvement in pathogenesis	ALL	[153, 154]
miRNA-129-2	• It is associated with lung adenocarcinoma and hepatocellular carcinoma through the control of cell growth • In head and neck squamous cell carcinoma with HPV positive and keratinocyte cells transfected with HPV, miRNA-129–2-3p shows increased expression • Given the growing understanding of the relationship between SARS-CoV-2 and comorbidities, changes in miRNA-129–2-3p expression could be of significant importance	Haematological malignancies, including lymphoma	[155]
Hypothesis*
miRNA-223-3p	• Capable of directly targeting NF-κB inhibitor alpha • Notch and NF-κB signaling pathways increase miRNA-223 transcription and decrease FBXW7 tumor suppressor transcription in T-cell ALL cases	ALL	[156]
miRNA-16 and miRNA-511	• miRNA-16 and miRNA-511 were significantly overexpressed in adult B-ALL	ALL	[157]
MSTRG.119845.30/hsa-miRNA-20a-5p/TNFRSF1B, MSTRG.119845.30/hsa-miRNA-29b-2-5p/FCGR2A, and MST RG.106112.2/hsa-miRNA-6501-5p/STAT3	• Investigating DEGs related to the immune and/or inflammatory response of the host and interaction networks of regulatory genes	Peripheral blood samples of COVID-19 patients	[158]
miRNA-155	• An essential role in the pathogenesis and severity of COVID-19 • Good diagnostic clinical biomarker for diagnosis of COVID-19 disease and severity of infection • A key target in cancer and an ideal target for therapeutic inhibition	DLBCL, AML, ALL and CLL	[159, 160]
miRNA-34a and miRNA-34a-5p	• Up-regulated mRNAs associated with cell proliferation interacted • Decreased expression of more than 30 distinct oncogenes in different cancer pathways (such as MET, MEK1, MYC, PDGFR-α, CDK4/6, BCL2, WNT 1/3, NOTCH1, CD44), along with genes that help tumors evade the immune system response (PD-L1, DGK)	Lymphoma, MM, and leukemias	[161, 162]
miRNA-125	• Related to the formation and growth of tumors, including proliferation of cancer cells, programmed cell death, invasion and dissemination to other parts of the body, metabolic activity, and immune reactions • Acts as an oncogenic factor or tumor suppressor gene and is also associated with drug resistance in various types of leukemia • Manages cervical cancer progression by controlling VEGF and PI3K/AKT signaling pathways	AML	[163, 164]
miRNA-223	• Reduce inflammation to prevent secondary damage during infection and prevent cancerous changes in myeloid cells • Targets of miRNA-223 involved in inflammation and infection include granzyme B, IKKa, Roquin, and STAT3 • In cancer, confirmed targets are C/EBPb, E2F1, FOXO1, and NFI-A • Viral nucleocapsid proteins can suppress BASCs and regulate the release of pro-inflammatory cytokines	AML, MM, and ALL	[156, 165]
miRNA- 150-5p	• It directly inhibits the translation of STAT5b mRNA, which leads to a decrease in total STAT5 protein phosphorylation and can be targeted therapeutically • Overexpression of cellular miRNA-150-5p, which is reduced in COVID-19 patients, can inhibit infection of SARS-CoV-2 target cells • Interaction between cellular miRNA-150-5p and a unique MRE in the NSP10 gene encoded by SARS-CoV-2	MM, AML, malignant lymphoma, Burkitt lymphomas	[166–168]
miRNA-21	• Alterations in miRNA-21 concentrations have the potential to modulate LZTFL1 gene expression, which may ultimately lead to organ fibrosis and inflammatory processes • This may provide valuable insights into the progression of severe symptoms associated with COVID-19 • miRNA-21 is effective in inducing apoptosis in cancer therapies targeting p53-deficient tumors • As miRNA-21 exhibits oncogenic properties, it presents an appealing target for the treatment of MM • Confirmed targets of miRNA-21 (PTEN, Rho-B, and BTG2) are associated with AKT dysfunction and extracellular signal-regulated kinase signaling	Haematological cancers (MM)	[169–171]
miRNA-29a	• Controls ACE2 and may play an important role in the initiation of COVID-19 infection • miRNA-29 participates in a signaling cascade that includes the phosphatase Ppm1d/Wip1, an important modulator of the DNA damage response, and the tumor suppressor p53 • Genes targeted for the regulation of programmed cell death such as the Bcl-2 family of proteins (cellular leukemia/lymphoma) • Dysregulation of the crucial anti-apoptotic protein Mcl-1 is frequently observed in cancerous cells	AML, CLL, MCL, and MM	[172–174]
miRNA-31	• Suppresses the expression of multiple pro-metastatic target genes, thus inhibiting various components of the invasion-metastasis process, including motility, invasion, and anoikis resistance • Significantly up-regulated microRNA in COVID-19 patients was miRNA-31-5p, which could be related to its function in regulating inflammation	CML	[175, 176]

Abbreviations: ALL Acute lymphoid leukemia, AML Acute myeloid leukemia, BASCs bronchoalveolar stem cells, CLL Chronic lymphocytic leukemia, CML Chronic myeloid leukemia, DEGs Differentially expressed genes, HPV Human papillomavirus, MCL Mantle cell lymphoma, MRE miRNA recognition element, MM Multiple myeloma, NSP10 nonstructural protein 10, NF-κB Nuclear factor kappa B

*Explanations about the function of miRNAs in various haematological malignancies or in COVID-19 raise hypotheses to find a new relationship between COVID-19 and miRNAs involved in the immune response in individuals with haematological malignancies exposed to this virus. It needs more studies and research