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. 2022 Jun;24(6):1086-1099.
doi: 10.1007/s12094-021-02751-1. Epub 2022 Jan 23.

Roles of circ_0000135/miR-140-3p/PDZK1 network in cervical cancer

N Wang #  1 , Y Zheng #  1 , X Zhang  1 , S W Xu  1 , X H Li  1 , Y L Meng  1 , J Q Liu  2
Affiliations

Roles of circ_0000135/miR-140-3p/PDZK1 network in cervical cancer

N Wang et al. Clin Transl Oncol. 2022 Jun.

Abstract

Purpose: To explore the effect of circ_0000135/miR-140-3p/PDZ domain containing 1 (PDZK1) on the occurrence and development of cervical cancer.

Methods: Clinical data were collected to verify circ_0000135/miR-140-3p/PDZK1 expression in cervical cancer. mRNA expressions of circ_0000135 and miR-140-3p were detected by real-time quantitative PCR. Correlation between circ_0000135 and miR-140-3p/miR-140-3p and PDZK1 was analyzed in vitro. Protein expression detection in cells was conducted by Western blot; while cell proliferation, invasion and cycle distribution by CCK8 assay, Transwell chamber assay and flow cytometry, respectively. Rescue and animal experiment were performed to verify the effect of circ_0000135/miR-140-3p/PDZK1 on cervical cancer.

Results: circ_0000135 and PDZK1 expressions were increased, while those of miR-140-3p were decreased in cervical cancer tissues and cells (both P < 0.05). sh-circ_0000135 group had decreased cell viability, arrested cells in G0/G1 phase, decreased CyclinD1 expression, inhibited cell migration and invasion; sh-circ_0000135 group showed reduced tumor volume, weight, and lower Ki67 expression (all P < 0.05). circ_0000135 had conserved target of miR-140-3p. There was a direct interaction between circ_0000135 and miR-140-3p. miR-140-3p might have direct interaction with PDZK1. sh-circ_0000135 and/or miR-140-3p treatment showed obviously decreased PDZK1 expression, decreased cell activity, arrested cells in G0/G1 phase, downregulated cell migration and invasion; sh-circ_0000135 and/or miR-140-3p mimic treatment showed obviously decreased tumor volume, tumor weight, and Ki67 expression (all P < 0.05).

Conclusion: circ_0000135 may play an anti-tumor role on the progression of cervical cancer by sponging miR-140-3p to suppress the expression of PDZK1, providing a promising therapeutic target.

Keywords: Cervical cancer; Invasion; PDZK1; Proliferation; circ_0000135; miR-140-3p.

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