MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer

Abstract

BackgroundCervical cancer is the second leading cause of death among female patients with cancer in the world. High risk human papillomavirus has causal roles in cervical cancer initiation and progression by deregulating several cellular processes. However, HPV infection is not sufficient for cervical carcinoma development. Therefore, other genetic and epigenetic factors may be involved in this complex disease, and the identification of which may lead to better diagnosis and treatment. Our aim was to analyze the expression of microRNAs in cervical cancer cases positive or negative for HPV E6/E7 mRNA, and to assess their diagnostic usefulness and relevance.MethodsThe expression of three different microRNAs (miR-9, miR-21, and miR-155) in 52 formalin-fixed paraffin-embedded (FFPE) primary cervical cancer tissue samples and 50 FFPE normal cervical tissue samples were evaluated.ResultsMiR-9, miR-21, and miR-155 were significantly overexpressed in cervical cancer tissues compared to normal tissues (P < 0.001). MiR-21 and miR-155 expression combined with the HPV E6/E7 mRNA assay in HPV E6/E7 negative cervical cancer showed increased AUC of 0.7267 and 0.7000, respectively (P = 0.01, P = 0.04), demonstrating their potential as diagnostic tools. Moreover, miR-21 and miR-155 were predictors showing a 7 fold and 10.3 fold higher risk for HPV E6/E7 negative patients with cervical cancer (P = 0.024 and P = 0.017, respectively) while miR-155 was a predictor showing a 27.9 fold higher risk for HPV E6/E7 positive patients with cervical cancer (P < 0.0001).ConclusionsThere is a strong demand for additional, alternative molecular biomarkers for diagnosis and management of precancer patients. MiR-21 and miR-155 may be helpful in the prediction of both HPV positive and HPV negative cases of cervical cancer.

Extracellular vesicle microRNA cargo is correlated with HPV status in oropharyngeal carcinoma

“…However, expression of the normally silent miR‐20b‐5p and other miRNA cluster members (miR‐106a‐5p and miR‐363‐3p) caused a decrease in proliferation in oral squamous cell carcinoma cells, highlighting the cancer‐specific role of certain miRNAs. We found an enrichment of miR‐9‐5p and miR‐9‐3p in HPV + EVs, which is consistent with reports of their overexpression in HPV + OPSCC and HPV + cervical cancer …”

Oncogenic microRNA signature for early diagnosis of cervical intraepithelial neoplasia and cancer

“…S1A), suggesting that RNU6B uniformly expressed in cervical tissue samples regardless of different disease status. Similar findings of using RNU6B as internal reference in miRNA expression studies in cervical lesions and cancer were also reported (Honegger et al, 2015;Park et al, 2017;Tian et al, 2014). After the relative quantification of miRNA expression was calculated, the fold change of the miRNA was analyzed using: 2 ÀDDCt .…”

“…No significant difference ( C t values) was found between three groups of samples ( P = 1.0, P = 0.26 and P = 0.08 for normal versus CIN, normal versus cancer and CIN versus cancer) (), suggesting that RNU6B uniformly expressed in cervical tissue samples regardless of different disease status. Similar findings of using RNU6B as internal reference in miRNA expression studies in cervical lesions and cancer were also reported (Honegger et al ., ; Park et al ., ; Tian et al ., ). After the relative quantification of miRNA expression was calculated, the fold change of the miRNA was analyzed using: .…”

The role of cancer-derived microRNAs in cancer immune escape

“…Lastly, cancer cells could escape immune attack by downregulating NKG2D ligands including MICA, MICB, and UL16-binding protein. TAP transporter associated with antigen processing, MHC-I major histocompatibility complex class I, MICA/B MHC-I chain-related molecules A/B, IDO indoleamine 2, 3-dioxygenase, ULBP UL16-binding protein cancer (NSCLC), and glioma might contribute to enhanced immune tolerance in the tumor microenvironment [57][58][59]. Meanwhile, some endoplasmic reticulum stress-associated miRNAs such as miR-346 regulates immune response by directly targeting TAP1 or indirectly suppressing the expression of MHC-I molecules and interferon (IFN) signaling pathway [60].…”