<p>Hsa_circ_103973 Acts as a Sponge of miR-335 to Promote Cervical Cancer Progression</p>

Abstract

Background: Cervical cancer (CC) ranks as the second most common malignancy in women, accounting for more two 2 million deaths every year in the world. Recently, circular RNAs (circRNAs) have been reported to regulate the progression of multiple human tumors; however, whether it involves in CC remains largely elusive. Materials and Methods: Two GEO circRNA expression profiles (GSE102686, GSE113696) were downloaded to analyze the differentially expressed circRNAs using bioinformatics methods. Expression of circ_103973, miR-335 and PPP6C in CC tissues and cell lines were examined by qRT-PCR. Cell apoptosis was assessed with PI/Annexin-V double staining followed by the analysis of flow cytometry. Cell proliferation was evaluated by MTT and colony formation assays. Interaction between circ_103973 and miR-335, as well as miR-335 and PPP6C, were verified by dual-luciferase reporter assay. Results: Circ_103973 was found to be highly expressed in both GSE102686 and GSE113696 datasets as well as in CC tissue samples and cell lines. Higher levels of circ_103973 were correlated to a worse outcome of CC patients. Knockdown of circ_103973 significantly promoted CC cell apoptosis and inhibited CC cell proliferation in vitro. Mechanistically, we demonstrated that circ_103973 served as a sponge of miR-335, which directly targeted PPP6C in CC cells. miR-335 was found to be decreased in CC, while PPP6C was found to be increased in CC. Moreover, anti-miR-335 could reverse the inhibitory effects of circ_103973 knockdown on CC cell proliferation, and this phenomenon could be blocked by si-PPP6C. Conclusion: Circ_103973 promoted CC cell proliferation in vitro by physically binding miR-335, which further targeted and regulated PPP6C.

Functions and Targets of miR-335 in Cancer

“… [ 47 ] Ovarian cancer BCL-W Apoptotic induction. [ 49 ] Cervical Cancer ROCK1 Proliferation inhibition [ 56 ] PPP6C Proliferation inhibition [ 70 ] Melanoma ROCK1 Proliferation inhibition [ 24 ] Osteosarcoma Survivin Apoptotic induction [ 37 ] ROCK1 Proliferation inhibition [ 59 ] Abbreviations : NSCLC, non-small cell lung cancer; ESCC, esophageal squamous cell carcinoma; CRC, colorectal cancer; HCC, hepatocellular carcinoma; RCC, renal cell carcinoma; EMC, endometrial cancer. …”

“… 47 In cervical cancer, miR-335 may inhibit cell proliferation by regulating protein phosphatase 6 catalytic subunit (PPP6C). 70 …”

“… [ 58 ] LncRNA NEAT1 HCC [ 82 ] LncRNA ZEB1-AS1 Gastric cancer. [ 42 ] LncRNA DANCR Osteosarcoma [ 59 ] LncRNA DANCR Cervical cancer [ 56 ] LncRNA SLCO4A1-AS1 Bladder cancer [ 48 ] LncRNA CASC9 NSCLC [ 29 ] LncRNA LINC01510 Thyroid carcinoma [ 65 ] LncRNA TINCR Ovarian cancer [ 113 ] LncRNA XIST NSCLC [ 64 ] LncRNA XIST Bladder cancer [ 110 ] lncRNA ZNRD1-AS1 Nasopharyngeal Carcinoma [ 72 ] CircRNA Circ-EIF4G3 Gastric cancer [ 70 ] Circ_103973 Cervical Cancer [ …”

“…Circ_103973 promotes cervical cancer cell proliferation by sponging miR-335, which further regulates PPP6C. 70 …”

Investigating the Underlying Mechanisms of Circular RNAs and Their Application in Clinical Research of Cervical Cancer

“…Circ_0000388 overexpression significantly hindered miR-337-3p expression and enhanced TCF12 expression to play a carcinogenic role in CC tissue and cells ( Meng et al, 2020 ). High expression of circ_103973 is also related to poor prognosis in CC patients, and circ_103973 is an miR-335 sponge that directly targets PPP6C in cells ( Zhu et al, 2020 ). The expression level of circRNA_0000285 was strongly higher than the corresponding normal tissues in CC samples.…”