Potential role of micro ribonucleic acids in screening for anal cancer in human papilloma virus and human immunodeficiency virus related malignancies

Table 1 Cellular micro ribonucleic acids deregulated by human papillomavirus proteins

HPV protein	miRNA target	miRNA expression level	Sample type	Biological effect(s)	Ref.
E5	miR-146a	+	E5-expressing HaCat cells	Promoted cell proliferation	[106]
	miR-203	-	E5-expressing HaCat cells	Increased expression of p63	[106]
	miR-324-5p	-	E5-expressing HaCat cells	Contributed to cervical carcinogenesis	[106]
E6	miR-20a	+	CaSki and SiHa (HPV16+) human cervical cell lines	Promoted cell growth through downregulating PDCD6 and activating Akt and p38	[156]
	miR-20b	+	HeLa (HPV18+), SiHa and Caski human cervical cancer cell lines; Cervical carcinoma tissues	Reduced TIMP2 expression and induced EMT, migration, and invasion	[157]
	miR-23b	-	SiHa and CaSki cell lines	Increased expression of uPA and induction of migration in human cervical cancer cells	[158]
	miR-30c-2*	-	HPV-infected NSCLC; TL1 cell line	Correlated with tumor stage and lymph node metastasis	[159]
	miR-34a	-	CaSki and SiHa cell lines, HPV18-positive cell lines HeLa and C411, HPV68-positive cell line ME180Cervical cancer tissues	Inhibited cell proliferation; Increased LDHA expression levels, inhibited Warburg effect and reprogrammed glycolysis through targeting LDHA	[160,161]
	miR-145	-	Hela, SiHa, and CaSki cell lines; Cervical cancer tissues	Modulated invasion and therapy resistance of cervical cancer cells	[162]
	miR-195	-	HeLa and SiHa cell line cervical cancer tissue samples	Promoted cell proliferation, invasion, and metastasis	[163]
	miR-218	-	HPV16 positive cervical cell lines and tissues; Cervical cancer tissues	Increased expression of LAMB3, SFMFBT1, and DCUN1D1, promoted EMT, migration, and invasion in cervical cancer associated with clinicopathological characteristics of patients	[164,165]
	miR-375	-	SiHa and CaSki cell lines; Cervical tissue samples	Modulated EMT in cervical cancer; Enhanced invasion and metastasis of cervical carcinoma cells through targeting SP1	[166,167]
	miR-2861	-	SiHa and CaSki cell lines; Cervical cancer tissues	Enhanced cell proliferation and invasion, and inhibited apoptosis in cervical cancer cells; Negatively associated with advanced tumor stage and lymph node metastasis	[168]
E7	miR-15b	+	HPV16 E7-expressing tumors from anal carcinoma patients; CaSki cell line	Downregulated cyclin E1; Increased expression of several E2F-regulated genes	[111]
	miR-20a	+	OSCC tissues	Inhibited cell proliferation, invasion, and migration	[169]
	miR-21	+	HPV16 E7-transfected Hela cells; Cervical cancer tissue	Enhanced cervical carcinoma cell proliferation, growth, and invasion; Involved in cervicitis and cervical cancer progression	[170,171]
	miR-25	+	HVK-derived raft tissues infected with either HPV16 or HPV18	Increased expression correlated with the progression of the cervical lesions, making it a potential biomarker for CINs and cervical cancer	[96]
	miR-27b	+	HPV 16-positive human cervical carcinoma tissues; SiHa and CaSki cell lines	Reduced PLK2 expression; Promoted cell proliferation and inhibited paclitaxel-induced cell apoptosis; Inhibited PPARγ expression and promoted proliferation and invasion	[172,173]
	miR-205	+	HPV-positive keratinocytes	Activated Akt pathway and upregulated cyclin D1 levels, resulting in increased proliferation	[174]
	miR-323	+	Cervical cancer cell lines transfected with HPV 16 E7 and SiHa cervical cancer cells	---	[175]
E6/E7	miR-16	+	HFK-derived raft cultures with HPV16 infection; HVK-derived raft tissues infected with either HPV16 or HPV18; CIN3 and Cervical carcinoma tissues with HR HPV infection	---	[96]
	miR-22	-	HVK-derived raft tissues infected with either HPV16 or HPV18	Suppressed tumor growth and metastasis	[96,176]
	miR-24	+	HPV-positive keratinocytes	Reduced p27 expression level and enhanced proliferation	[174]
	miR-29a	-	HVK-derived raft tissues infected with either HPV16 or HPV18	---	[96]
	miR-92a	+	CIN and cervical carcinoma tissues with HR HPV infection, and raft tissues with HPV16 or HPV18 infection	Increased expression correlated with the progression of the cervical lesions, and may serve as a biomarker for CINs and cervical cancer	[96]
	miR-100	-	HFK-derived raft cultures with HPV18 infection	---	[96]
	miR-125a	-	Cervical carcinoma tissuesSiHa and HeLa cell lines	Increased STAT3 expression and enhanced tumorigenesis and metastasis	[177]
	miR-146a-5p	-	HPV16 E6/E7-positive keratinocytes; Hela, SiHa, and CaSki cell lines	Enhanced expression of KDM2B; Promoted proliferation and migration	[178]
	miR-203	-	NHKs and NFKs expressing E6, E7, or combination	Increased expression of p63 and promotion of cell proliferation	[179,180]
	miR-378	+	CIN3 and cervical carcinoma tissues with HR HPV infection, and raft tissues with HPV16 or HPV18 infection	---	[96]

“+”: Upregulated; “-”: Downregulated; miRNAs: Micro ribonucleic acid; HPV: Human papillomavirus; PDCD6: Programmed cell death 6; TIMP-2: Tissue inhibitor of metalloproteinase 2; EMT: Epithelial to mesenchymal transition; NSCLC: Non-small cell lung cancer; LDHA: Lactate dehydrogenase A; LAMB3: Laminin 5 β3; SFMFBT1: Scm-like with four MBT domains 1; DCUN1D1: Defective in cullin neddylation 1; Domain containing 1; OSCC: Oral squamous cell carcinoma; HVK: Human vaginal keratinocytes; PLK2: Polo-like kinase2; CIN: Cervical intraepithelial neoplasia; HFK: Human foreskin keratinocytes; CIN3: Cervical intraepithelial neoplasia 3; HR HPV: High risk HPV.

Table 2 Cellular micro ribonucleic acids deregulated during human immunodeficiency virus infection

Sample type	miRNAs deregulated	Ref.
PBMCs from HIV-infected patients	↑ miR-9; ↓ miR-29c, miR-31, miR-125b, miR-146b-5p, miR-150, Let-7g	[181]
T cells from HIV-infected individuals	↓ miR-16, miR-146b, miR-150, miR-223	[182]
HIV-1 infected PBMCs	↑ miR-223; ↓ miR-21, miR-26a, miR-29a, miR-29b, miR-29c, miR-155	[183]
HIV-1 infected PBMCs	↑ miR-3195, miR-3656, miR-4492, and miR-6087; ↓ miR-1273h-3p, miR-1273h-5p, miR-671-5p, and miR-7-5p	[118]
HIV-2-infected PBMCs	↑ miR-18a-3p and hsa-miR-320b	[118]
HIV-2-infected MDMs	↑ miR-542-3p, miR-375, miR-195-5p, miR-30c-2-3p, miR-4802-3p, and miR-26b-5p	[118]
HIV-1- and HIV-2-infected MDMs	↓ miR-148b-5p, hsa-miR-26a-2-3p, miR-199a-1, miR-199a-2, and miR-874-5p	[118]
HIV-1-transfected HeLa cells	↓ miR-16, miR-93, miR-148b, miR-221	[184]
HIV-1 infected Jurkat cells.	↑ miR-122, miR-297, miR-370, and miR-373; ↓ miR-17-5p and miR-20a	[185]
latently infected CD4+ T cells	↑ miR-196b and miR-1290	[186]
PBMCs obtained from HIV-1 positive individuals with high viral load	↑ miR19b, miR-34a, miR-144, miR-146a, miR-155, miR-382, miR-615-3p	[187]
Plasma obtained from patients with HIV infection	↓ miR-3162-3p	[188]
HIV-1-infected HUT78 cells and CD4+ T cells from chronic HIV-1 infected individuals	↓ Let-7 miRs	[189]
HIV-1 positive plasma samples in the acute stage infection	↑ miR-16-5p, miR-20b-5p, miR-24-3p, miR-142-5p, miR-195-5p, miR-206, miR-223-3p, miR-885-5p, and let-7 g-3p; ↓ miR-34c-3p, miR-181c-3p, miR-202-3p, and miR-409-3p	[190]
HIV-1 infected CD4+ T cells	↓ miR-20a and miR-106b	[191]

↑: Upregulation; ↓: Downregulation; miRNAs: Micro ribonucleic acid; HIV: Human Immunodeficiency virus; PBMC: Peripheral blood mononuclear cells; MDM: Monocyte-derived macrophages.

Table 3 Cellular micro ribonucleic acids deregulated by human Immunodeficiency virus proteins

HIV protein	miRNA target	Effect	Sample type	Biological effect	Ref.
Tat	miR-21, miR-29a, miR-222, miR-1290	+	Tat101-expressing Jurkat cells; Resting PBMCs from healthy donors were transiently transfected with Tat101-expressing vector	Targeted mRNAs of genes involved in apoptosis, T cell migration, and proliferation	[192]
	miR-128a, and miR-3182	-	Tat101-expressing Jurkat cells	----	[192]
	miR-132	+	Tat-transfected astrocytes and neurons, astrocytes from Tat-transgenic mice, and HIV-infected astrocytes	Involved in the direct neurotoxicity of Tat	[193]
	miR-129, miR-135a, miR-181a, miR-495, miR-523, miR-524, miR-539, let-7	-	U-87MG (astrocyte cell line), HEK 293T, and HeLa cells transfected with wild-type Tat	Downregulation of β-catenin activity	[194]
	miR-101	+	BMVECs exposed to Tat C	Decreased the expression of VE-cadherin	[195]
	miR-34a and miR-138	+	Astrocytoma cell line A172 and rat primary astrocytes exposed to Tat	Upregulated NF-κB and promoted activation of astrocytes	[196]
Nef	miR-573 and miR-638	+	Human monocytic U937 cells that stably expressed HIV-1 Nef	Altered several pathways involved in HIV pathogenesis	[197]
	miR16-1, miR-18, miR-19a, miR-20a, miR-21, miR-27a, miR-29b, miR-125b, miR-146a, miR-146b-3p, miR-181a, miR-223, miR-570, miR-610 and miR-624	-	Human monocytic U937 cells that stably expressed HIV-1 Nef	Altered several pathways involved in HIV pathogenesis	[197]
	miR-17, miR-19a, miR-19b, miR-20a, miR26a, miR-28, miR-29a, miR-29b, miR-29c, miR-92a, miR-125b, miR-149, miR-150, miR-223, miR-324-5p, miR-378 and miR-382	+	Nef exosomes	Inhibited HIV replication	[197]
Vpr	miR-942-5p	+	PEL cells	Targeted IκBα and activation of NF-κB signalling	[198]
	miR-711	+	PEL cells	Directly targeted Notch1 and reduced levels of IκBα transcript	[198]

“+”: Upregulation; “-”: Downregulation; miRNA: Micro ribonucleic acid; HIV: Human Immunodeficiency virus; HEK: Human embryonic kidney cells; BMVEC: Human brain microvascular endothelial cells; PEL: Primary effusion lymphoma; NF-κB: NF-kappaB inhibitor.