Background and purpose: Piwil2 is highly expressed in precancerous and cancer stem cells

which plays a key role in the process of tumorigenesis and progression through the transcriptional and post-transcriptional regulation of gene expression. This study aimed to elucidate the role of Piwil2 in regulating the malignant process of cervical cancer. Methods: In order to generate cell line with overexpression or silence of Piwil2

HeLa and SiHa

cells were transfected with lentiviral pLenti-CMV-Piwil2-SV40-EGFP or plasmid shPiwil2

respectively. Cell proliferation assays using CCK-8 were performed in 96-well format in duplicate. Cell cycle and side population (SP) cells were analyzed by fluorescence-activated cell sorting (FACS). The proteins related to cell growth and cell cycle were measured by Western blot. CCK-8 assay was also used to assess the killing effects of cisplatin. Results: Overexpression of Piwil2 promoted cervical cancer cell proliferation and the entry of cells from G

0

/G

1

phase into S phase

as compared to the control cells (P0.05). On the contrary

Piwil2 knockdown suppressed proliferation of both cells and increased the number of cells during G

0

/G

1

phase markedly (P0.05). Western blot analyses confirmed that Piwil2 overexpression led to an upregulation of cyclin D1 and p-Stat3 but a significantly decreased level of p53. Furthermore

overexpression of Piwil2 significantly increased the SP cell populations in both HeLa and SiHa cells (P0.01)

sequentially enhanced resistance in cancer cells to cisplatin (P0.01). Instead

Piwil2 gene knockdown induced an apparent downregulation of cyclin D1 and p-Stat3

significantly increased p53 expression

and decreased proportion of SP cells

which

to some extent

contributed to the improved sensitivity to cisplatin. Conclusion: Piwil2 plays an essential role in the progression of cervical cancer via increasing the proportion of SP cells. Therefore

targeting Piwil2 may be an effective therapeutic option for patients with cervical cancer.