Upregulation of lncRNA CALML3-AS1 promotes cell proliferation and metastasis in cervical cancer via activation of the Wnt/β-catenin pathway

C.-N. Liu, H.-Y. Zhang, C.-L. Liu, C.-C. Wang

Department of Gynecology, Clinical Laboratory, Linyi Cancer Hospital, Linyi, Shandong, China. opoww216@126.com

---

• Oncology

OBJECTIVE: It is well verified that lncRNA are emerging as imperative regulators in various tumors. LncRNA CALML3-AS1 (CALML3-AS1), a freshly discovered lncRNA, has been confirmed as a tumor promoter in bladder cancer. This present study aimed to explore the biological functions and molecular mechanisms of CALML3-AS1 in cervical cancer (CC).

PATIENTS AND METHODS: We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) datasets to determine dysregulated lncRNAs in CC. Real Time-Polymerase Chain Reaction (RT-PCR) was applied for the assays of CALML3-AS1 amplification in CC samples and cell lines. Kaplan-Meier analysis and multivariate assays were carried out for determination of the prognostic values. The functions of CALML3-AS1 on cell proliferation, invasion, migration, and apoptosis were determined by a series of cells experiments by knocking down CALML3-AS1. MRNA and protein expressions of signaling pathways were examined using Western blot.

RESULTS: We found that CALML3-AS1 was upregulated in CC tissues and this upregulation was associated with FIGO stage, histological grade, and reduced overall survival. Multivariate assays indicated that high CALML3-AS1 expression was an independent prognostic parameter indicating poorer clinical outcome for CC patients. Functional assays suggested that knockdown of CALML3-AS1 suppressed the proliferation, migration, and invasion of CC cells, and induced apoptosis. Mechanistic investigations revealed that inhibiting the expression of CALML3-AS1 decreased the levels of β-catenin, cyclin D1, and c-myc via Western blot.

CONCLUSIONS: Our study revealed that CALML3-AS1 could be an oncogenic lncRNA promoting the growth and metastasis of CC by modulating Wnt/β-catenin pathway, suggesting that CALML3-AS1 may be an important contributor to CC progression.

Free PDF Download