Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

Abstract

Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development.

Expressions and clinical significance of autophagy-related markers Beclin1, LC3, and EGFR in human cervical squamous cell carcinoma

“…However, high clinical TNM stage and lymph node metastasis have been identified in Beclin1- and LC3-negative patients with positive high-risk human papillomavirus (HPV) infection. 20 Similar results have been observed in other cancer types. For instance, Jiang et al found that Beclin1 and LC3 expression were not associated with the age, sex, smoking, histological type, lymph node metastasis, or TNM stage of lung cancer patients.…”

Autophagy in malignant transformation and cancer progression

“…Accordingly, epithelial cells bearing molecular defects in the autophagic machinery, such as those provoked by Crohn's disease‐associated point mutations in ATG16L1 and nucleotide‐binding oligomerization domain containing 2 ( NOD2 ) (Lassen et al , ), are more susceptible to infection by intracellular pathogens than their wild‐type counterparts. In line with this notion, reduced levels of autophagic markers including BECN1 have recently been correlated with HPV‐16 and HPV‐18 infection in a cohort of cervical carcinoma patients (Wang et al , ). Thus, autophagy may exert oncosuppressive effects also by virtue of its antiviral and antibacterial activity.…”

The potential of Beclin 1 as a therapeutic target for the treatment of breast cancer

“…Targets (2015) 20 (2) dependent degradation of mutant p53 could induce reactivation of wild-type p53 function and inhibit malignant transformation. In a cohort of uterine cervical cancer patients, human papilloma virus (HPV) 16 and HPV18 infection was associated with reduced levels of Beclin 1 expression, which might suggest a potential role for Beclin 1 as a defense against oncogenic virus infection [68].…”