Research article
Long non-coding RNA ABHD11-AS1 facilitates the progression of cervical cancer by competitively binding to miR-330–5p and upregulating MARK2

https://doi.org/10.1016/j.yexcr.2021.112929Get rights and content

Highlights

  • ABHD11-AS1 actuates CC cell proliferation, migration and invasion and restrained cell apoptosis.

  • ABHD11-AS1 sponges miR-330–5p in CC cells.

  • Knockdown of miR-330–5p reverses the inhibiting effect of down-regulating ABHD11-AS1 on CC progression.

  • MARK2 is targeted by miR-330–5p and negatively associated with miR-330–5p.

  • ABHD11-AS1 accelerates the progression of CC through upregulating MARK2.

Abstract

Cervical cancer (CC) is among the most prevalent gynecological malignancies. Participation of long non-coding RNA (lncRNA) in modulating biological behaviors of CC cells has been confirmed. However, the function of lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) in CC is still unclear. RT-qPCR and Western blot were performed for measuring RNA and protein levels. Functional assays were done to evaluate ABHD11-AS1 influences on cell proliferation, apoptosis, invasion and migration. After the verification of ABHD11-AS1 distribution in CC cells, mechanism assays were conducted to study the interaction of relative RNAs. ABHD11-AS1 expression was abnormally high in CC cells. In vitro experiments showed ABHD11-AS1 downregulation restrained CC cell malignant phenotypes. In vivo experiments proved ABHD11-AS1 knockdown impeded tumor growth. Moreover, miR-330–5p was corroborated to bind with ABHD11-AS1 in CC cells and microtubule affinity regulating kinase 2 (MARK2) was confirmed to be targeted by miR-330–5p. MiR-330–5p inhibition or MARK2 overexpression could countervail the suppressive effect of ABHD11-AS1 knockdown on CC cell malignant behaviors. We found that ABHD11-AS1 facilitated CC tumorigenesis through competitively sequestering miR-330–5p to upregulate MARK2, indicating ABHD11-AS1 as a potential biomarker in CC.

Section snippets

Background

As the primary malignant tumor of the cervix, cervical cancer (CC) is among the most prevalent gynecological malignant tumors, which threatens the health of women around the globe [1]. CC is the second leading cause of death among female malignancies in China [2]. About 130,000 women in China are diagnosed with CC every year with about 53,000 deaths [3]. Besides human papillomavirus (HPV) which is regarded as the most critical etiological element in CC development, genetic variations also play

Cell culture

Human CC cell line HeLa, human papillomavirus (HPV)-18 immortalized cell line, CaSki (HPV16-positive CC cell line), C-33A (HPV-negative CC cell line), HCC94 (well-differentiated CC cell line) and the normal cervical epithelial cell line (End1/E6E7) were utilized for our study. End1/E6E7, HeLa, C-33A and CaSki cells were purchased from American Type Culture Collection (ATCC) (Manassas, VA, USA). HCC94 cells were brought from Procell Life Science & Technology Co., Ltd. (Wuhan, China). End1/E6E7

ABHD11-AS1 depletion attenuates CC cell malignant behaviors

First, since ABHD11-AS1 is an antisense lncRNA, we identified its full-length sequence by 5′ and 3’ RACE experiment, and the results were shown in Fig. S1A. Then, to explore the association between ABHD11-AS1 and CC in vitro, we detected ABHD11-AS1 expression in different cell lines. Supported by the results of RT-qPCR, we found that ABHD11-AS1 level in CC cell lines (HCC94, HeLa, C-33A and CaSki) was higher than End1/E6E7 cells (Fig. 1A). Later, functional assays were implemented with the

Discussion

Cervical cancer (CC) is a notorious malignancy with high morbidity and mortality prevalent in the whole world [1]. With the wide coverage of early screening and the development of treatment, the survival rate of CC patients has risen. Nevertheless, for advanced patients, the overall treatment efficacy is still not ideal [5], indicating a demand for consistent molecular research on CC progression. For the past few years, a great number of lncRNAs were found to be correlated with CC development [

Conclusions

In sum, our study elucidated that ABHD11-AS1 sponged miR-330–5p to upregulate MARK2 so as to facilitate cell growth, migration, invasion and decline apoptosis of CC cells. Though clinical samples were not involved, the current study could still offer a novel sight for understanding CC.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

Not applicable.

Authors’ contributions

SH designed this study. SH, XZ and JY performed experiment, prepared figures, interpreted data. JY wrote the draft. All authors have read and approved the manuscript.

Funding

This work was supported by Clinical Medical Centers of Suzhou (SZZX201505); Introduce Project of Clinical Medical Experts of Suzhou (SZYJTD201707); Suzhou Municipal Hospital Gynecological Clinical Trial and Improvement Project (SLT201955); Suzhou Science and Technology Project (SYSD2018124).

A. RT-qPCR tested ABHD11-AS1 expression in CC cells (HCC94, HeLa, C-33A, and CaSki) versus normal control cells (End1/E6E7). B. ABHD11-AS1 expression was quantified via RT-qPCR in CC cells with transfection

Declaration of competing interest

None.

Acknowledgments

We are very grateful for the support of the laboratory and the help of the team colleagues.

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