LncCDCA3L inhibits cell proliferation via a novel RNA structure‐based crosstalk with CDCA3 in hepatocellular carcinoma

Abstract

Background & Aims The molecular mechanisms underlying hepatocellular carcinoma (HCC) remain poorly understood. In this study, we investigated cell division cycle‐associated 3 (CDCA3) expression status and characterized a CDCA3‐related long non‐coding RNA (lncRNA) in HCC. Methods RT‐qPCR and western blot were used to determine CDCA3 expression level in HCC clinical specimens. 5′ and 3′‐RACE, RNAscope, RNA pull‐down, CRISPR/Cas9‐based RNA immunoprecipitation (CRIP) and site‐directed mutation experiments were used to characterize lncCDCA3L and investigate its function target. Chi‐square test and Kaplan–Meier analysis were used to assess lncCDCA3L clinical significance. The effects of lncCDCA3L on HCC development were assessed by overexpression in vitro and in vivo. Results In this study, we found CDCA3 was a potential oncogenic factor in HCC and characterized the lncCDCA3L, which could inhibit CDCA3. LncCDCA3L is significantly downregulated in HCC and its expression level is associated with tumour size and can act as an independent risk factor affecting postoperative survival time in HCC patients. Mechanistically, lncCDCA3L can repress CDCA3 protein level and inhibit hepatocarcinogenesis by directly binding to CDCA3 mRNA at 1423–1455 region via a novel manner based on a hairpin structure motif. Conclusions Our study collectively unveiled the molecular mechanisms of how lncCDCA3L repressed the tumourigenic properties of HCC cells and exhibited a tumour suppressor character in HCC in a CDCA3‐dependent manner. The findings here support lncCDCA3L can be used as a candidate prognostic biomarker for HCC patients.

A Novel Ferroptosis-Related Signature for Prediction of Prognosis, Immune Profiles and Drug Sensitivity in Hepatocellular Carcinoma Patients

“…We created nFRGs consisting of seven ferroptosis-related genes, including CDCA3, NQO1, STMN1, AURKA, G6PD, NT5DC2, and SLC7A11. CDCA3 has been demonstrated to be among the potential carcinogenic factors for HCC [ 36 ]. NQO1 promotes the invasion of HCC by amplifying the ERK-NRF2 signaling pathway [ 37 ].…”

Prognostic value of cell division cycle-associated protein-3 in prostate cancer

“…[5] CDCA3 is a part of the Skp1/Cullin 1/F-box (SCF) ubiquitin ligase (E3) protein complex, which effectively degrades tyrosine kinase wee1 and modulates cell cycle. [5][6][7] Moreover, CDCA3 emerges with up-regulated expression in a variety of cancers, such as bladder urothelial carcinoma, [8] colorectal cancer, [9] non-small cell lung cancer, [10] hepatocellular carcinoma, [11] and ovarian cancer, [12] and plays a critical role in promoting tumor progression. CDCA3 also has been found to be a good biomarker candidate to predict the prognosis of renal cell carcinoma and kidney renal papillary cell carcinoma patients.…”