Long non-coding RNA LINC01554 overexpression suppresses viability, migration, and invasion of liver cancer cells through regulating miR-148b-3p/EIF4E3.

Background: Long non-coding RNAs (lncRNAs) can be severed as competing endogenous RNAs (ceRNAs) to regulate target genes or mRNAs via sponging microRNAs (miRNAs). This study explored the effect of LINC01554 on liver cancer cells through the ceRNA mechanism. Methods: Five significantly down-regulated lncRNAs were selected for further verification, and then through bioinformatics, interactive miRNAs and mRNAs of lncRNAs were identified. The relationship between LINC01554, miR-148b-3p and EIF4E3 was detected by the dual luciferase reporter gene assay. Afterwards, HCCLM3 cells were transfected with pCDH-LINC01554, miR-148b-3p inhibitor and miR-148b-3p mimics. Cell viability, apoptosis, migration and invasion were measured by Cell Counting Kit-8, flow cytometer, and Transwell assays. Real-time quantitative PCR (RT-qPCR) and Western blot were used to measure the expressions of related genes and proteins. Results: LINC01554 was significantly down-regulated in the liver cancer cell lines, and was expressed in the cytoplasm of HCCLM3 cells. LINC01554 overexpression inhibited proliferation, migration, and invasion of HCCLM3 cells, and promote their apoptosis (P < 0.05). Besides, LINC01554 overexpression also significantly increased the levels of BAX, BCL2/BAX, P53, cleaved-Caspase3, TIMP3, E-cadherin and EIF4E3 (P < 0.05). Through bioinformatics and dual-luciferase reporter gene assay, LINC01554, miR-148b-3p and EIF4E3 were proved to interact with each other. Furthermore, the effects of miR-148b-3p knockdown on HCCLM3 cells were similar with those of LINC01554 overexpression, and miR-148b-3p mimics could reverse the changes of cell viability, apoptosis, migration, and invasion induced by LINC01554 overexpression. Conclusions: LINC01554 overexpression could suppress the growth and metastasis of HCCLM3 cells via miR-148b-3p/EIF4E3.

Characterization of LIMA1 and its emerging roles and potential therapeutic prospects in cancers.

Actin is the most abundant and highly conserved cytoskeletal protein present in all eukaryotic cells. Remodeling of the actin cytoskeleton is controlled by a variety of actin-binding proteins that are extensively involved in biological processes such as cell motility and maintenance of cell shape. LIM domain and actin-binding protein 1 (LIMA1), as an important actin cytoskeletal regulator, was initially thought to be a tumor suppressor frequently downregulated in epithelial tumors. Importantly, the deficiency of LIMA1 may be responsible for dysregulated cytoskeletal dynamics, altered cell motility and disrupted cell-cell adhesion, which promote tumor proliferation, invasion and migration. As research progresses, the roles of LIMA1 extend from cytoskeletal dynamics and cell motility to cell division, gene regulation, apical extrusion, angiogenesis, cellular metabolism and lipid metabolism. However, the expression of LIMA1 in malignant tumors and its mechanism of action have not yet been elucidated, and many problems and challenges remain to be addressed. Therefore, this review systematically describes the structure and biological functions of LIMA1 and explores its expression and regulatory mechanism in malignant tumors, and further discusses its clinical value and therapeutic prospects.

CircCCDC66: Emerging roles and potential clinical values in malignant tumors.

Circular RNAs (circRNAs) are endogenous non-coding RNAs (ncRNAs) with a closed-loop structure. In recent years, circRNAs have become the focus of much research into RNA. CircCCDC66 has been identified as a novel oncogenic circRNA and is up-regulated in a variety of malignant tumors including thyroid cancer, non-small cell carcinoma, gastric cancer, colorectal cancer, renal cancer, cervical cancer, glioma, and osteosarcoma. It mediates cancer progression by regulating epigenetic modifications, variable splicing, transcription, and protein translation. The oncogenicity of circCCDC66 suppresses or promotes the expression of related genes mainly through direct or indirect pathways. This finding suggests that circCCDC66 is a biomarker for cancer diagnosis, prognosis assessment and treatment. However, there is no review on the relationship between circCCDC66 and cancers. Thus, the expression, biological functions, and regulatory mechanisms of circCCDC66 in malignant tumor and non-tumor diseases are summarized. The clinical value and prognostic significance of circCCDC66 are also evaluated, which can provide insights helpful to those exploring new strategies for the early diagnosis and targeted treatment of malignancies.