An increase of microRNA‑16‑1 is associated with the high proliferation of squamous intraepithelial lesions in the presence of the integrated state of HR‑HPV in liquid cytology samples

Abstract

Studies of cervical cancer (CC) have reported that microRNA-16-1 (miR-16-1), which is an oncomiR, is increased in the tissues and cell lines of CC. The aim of the present study was to investigate the association of miRNA-16-1 expression level with squamous cell carcinoma (SCC), the presence of squamous intraepithelial lesions (SIL) and the integration of high-risk human papillomavirus (HR-HPV) DNA. The current study analyzed 80 samples obtained from women by liquid-based cytology, which revealed that 20 were negative for SIL (NSIL) and without HPV, 20 were low-grade SIL (LSIL), 20 were high-grade SIL (HSIL), and 20 were diagnosed as SCC with HR-HPV. The genotyping of the viral DNA was conducted via an INNO-LiPA-HPV array, the expression of miR-16-1 was determined by reverse transcription-quantitative PCR, and the physical state of the HR-HPV was ascertained by in situ hybridization with amplification with tyramide. A total of eight HR-HPV genotypes were distinguished; the most frequent of these being HPV16, followed by multiple infection with HR-HPV (including HPV16). The mixed state of the HR-HPV was observed in 60 and 65% of LSIL and HSIL cases, respectively, while an integrated HR-HPV state was identified in 90% of cases with SCC. The expression level of miR-16-1 increased according to the grade of SIL, and cases with HSIL exhibited a significantly higher miR-16-1 expression level compared with women with NSIL (P<0.001; Table II). It can therefore be determined that the expression of miR-16-1 effects cellular proliferation, due to the viral integration of various HR-HPV genotypes in unique infection or in multiple infection. Thus, the overexpression of miR-16-1 could be monitored in women with LSIL, in order to discard a major lesion.

The Dysregulation of MicroRNAs in the Development of Cervical Pre-Cancer—An Update

“…The expression of miR-16-1 increased with the progression of the SIL. The expression of miR-16-1 in patients with HSIL was significantly higher than that in normal patients [6]. Nevertheless, when the expression level of miR16-1 in LSIL was compared with that in normal conditions a slight increase was identified, but it was not statistically significant.…”

“…In order to recognize the role of miRNAs in the initiation and early progression of cervical cancer, multiple research studies using HSIL and LSIL samples were performed [6,13,[31][32][33][34][35]. They consistently concluded that dysregulation of miRNAs' expression could explain the progression of SIL from normal cervical tissue.…”

“…However, the review did not focus on the association of those in the cervical pre-cancer stage. Indeed, several studies have demonstrated that the dysregulation of miRNAs' expression was correlated with HPV infection in cervical pre-cancer [5][6][7][8][9]12,16,19,26,28,38,39].…”

“…With HPV integrated, miR-16-1 expression increases around ~7 fold when compared to HPV-negative samples. However, as all HPV-negative samples were normal samples, and after adjustment, variability in the expression level of miR-16-1 induced by SIL and SCC outweighs those by HPV physical state [6].…”

“…SIL would gradually develop into squamous cell carcinoma (SCC) [5]. Squamous cell carcinoma accounts for 70-80% of cervical cancer and is the most common type of cervical cancer [6]. Compared to the cytology test, which is only a screening test, biopsy results which classifies CIN into CIN1, CIN2, and CIN3 describe the actual changes in the cells.…”