Aldehyde dehydrogenase 1, a target of miR‑222, is expressed at elevated levels in cervical cancer

Abstract

The aim of the present study was to investigate the expression of microRNA-222 (miR-222) and aldehyde dehydrogenase 1 (ALDH1) in tissues and peripheral blood of cervical cancer patients, and to elucidate their underlying mechanisms of action. Tumor tissues and tumor-adjacent tissues were obtained from 33 cervical cancer patients and peripheral blood was obtained from these patients and 28 healthy subjects. The expression of miR-222 and ALDH1 mRNA was evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To examine the levels of ALDH1 protein in tissues and blood, western blotting and ELISA were used. To confirm a direct interaction between miR-222 and ALDH1 mRNA, a dual luciferase reporter assay was performed. HeLA cells were transfected with agomiR-222 and expression of ALDH1 in the cells was measured by RT-qPCR and western blotting. MTT assay was preform to investigate the proliferation of HeLA cells. Expression of ALDH1 mRNA and protein was elevated in cervical cancer tissues and peripheral blood from patients compared with tumor-adjacent tissues and healthy controls, while the expression of miR-222 was reduced. Upregulation of miR-222 inhibited HeLA cell proliferation possibly due to a reduction in the expression of ALDH1. A dual luciferase reporter assay showed that miR-222 can bind with the 3'-untranslated seed region of ALDH1 mRNA to regulate its expression. miR-222 regulation of ALDH1 expression may play a role in the prevention of cervical cancer.

ITGA7, CD133, ALDH1 are inter‐correlated, and linked with poor differentiation, lymph node metastasis as well as worse survival in surgical cervical cancer

“…Some specific examples are as follows: in rectal cancer patients, ITGA7 overexpression correlates with higher pathological grade, larger tumor size, and advanced T stage 27 ; in breast cancer, ITGA7 overexpression is associated with higher TNM stage and pathological grade 28 ; what is more, another study illustrates that elevated expression of ITGA7 in OSCC tissues links with poor differentiation and higher risk of lymph node metastasis 9 . In terms of CD133 and ALDH1, their overexpression also correlates with advanced clinicopathological properties in multiple cancers 14,22,24,29,30 . In the present study, overexpression of ITGA7 and ALDH1 was correlated with poor differentiation and higher occurrence of lymph node metastasis.…”

“…Possible reason would be that ITGA7 might serve as an oncogene, which inhibits the cell apoptosis as well as induces the cell metastasis and invasion via activating FAK/Akt signaling or binding with S100 calcium‐binding protein, besides ITGA7 is proved to be linked with CSC activity in many other neoplasms 9–13,26 . In the meantime, CD133 and ALDH1 are tumor initiating genes and also serve as CSC surface markers according to the evidence mentioned above 24,25 . Therefore, ITGA7 expression is positively correlated with the expression of CD133 and ALDH1.…”

“…[9][10][11][12][13]26 In the meantime, CD133 and ALDH1 are tumor initiating genes and also serve as CSC surface markers according to the evidence mentioned above. 24,25 Therefore, ITGA7 expression is positively correlated with the expression of CD133 and ALDH1.…”

“…Whereas, the role of ITGA7 in regulating the stemness of cervical cancer cells thus further acting as a potential biomarker for the prognosis in cervical cancer patients remains elusive. Interestingly, in terms of cervical cancer, previous studies illustrate that CD133 and ALDH1 are associated with tumor stemness and further relate to the poor prognosis in cervical cancer 14,15,22–25 . To be specific, CD133 is reported to facilitate the proliferation of CSC and initiate tumor growth in cervical cancer pathology 14,15,22,23 .…”

“…7 ITGA7, CD133, and ALDH1 mediate the CSC properties in multiple carcinomas. 9,[11][12][13][14]22,24,29,30 Therefore, overexpression of ITGA7, CD133, and ALDH1 might be correlated with poor differentiation in cervical cancer pathology. So far, former studies have revealed the correlation of ITGA7 expression with prognosis for various neoplasms.…”