Crosstalk between lncRNA DANCR and miR-125b-5p in HCC cell progression

Abstract

Objective: To investigate the mechanism of long noncoding RNA (lncRNA) DANCR on the progression of hepatocellular carcinoma (HCC) cells. Methods: The expression levels of DANCR and miR-125b-5p were measured in normal hepatocytes (LO2) and HCC cell lines by quantitative reverse transcription polymerase chain reaction. HepG2 and Huh-7 cells were transfected with sh-DANCR, the negative control (sh-NC), miR-125b-5p mimic, or mimic NC or cotransfected with sh-DANCR and miR-125b-5p inhibitor. HCC cell proliferation was assessed through CCK8 and plate colony formation assay. Western blot quantified the expression levels of Bcl-2, Bax, caspase-3, and cleaved-caspase-3. Apoptotic rate was detected as well as migratory and invasive capacities. The implication of the MAPK signal pathway was assessed by detecting the expression levels of p38, ERK1/2, JNK, p-p38, p-ERK1/2, and p-JNK. Interactions between DANCR and miR-125b-5p were detected by dual luciferase reporter assay. Results: In HCC cells, DANCR was highly expressed and miR-125b-5p was decreased. sh-DANCR or miR-125b-5p mimic stimulation reduced HepG2 or Huh-7 cell progression while promoted cell apoptosis evidenced by increased apoptotic rate, elevated levels of Bax and cleaved-caspase-3, and decreased Bcl-2. Moreover, the migration rate and invasiveness of HCC cells were also inhibited by sh-DANCR and miR-125b-5p mimic. Levels of p-p38/p38, p-ERK1/2/ERK1/2, and p-JNK/JNK were suppressed by sh-DANCR and miR-125b-5p mimic. LncRNA DANCR negatively targeted and directly bound to miR-125b-5p. Knockdown of miR-125b-5p could reverse the inhibitory effects of sh-DANCR on HCC cells. Conclusion: In HCC cells, lncRNA DANCR sponges miR-125b-5p and activates MAPK pathway, thus facilitating HCC cell progression.

The lncRNA DANCR promotes development of atherosclerosis by regulating the miR-214-5p/COX20 signaling pathway

“…These data revealed that DANCR downregulation could efficiently reduce the inflammatory response and oxidative stress during AS progression, contributing to our understanding of the pathogenic mechanism during AS development. In addition, DANCR has been identified as the ceRNA of several target miRNAs other than miR-214-5p, such as miR-185-5p [32], miR-874-3p [33], miR-1301-3p [34], miR-185-5p [35], miR-345-5p [36], miR-125b-5p [37], and miR-144-3p [38]. Since one lncRNA might target one or more downstream miRNAs [39], we hypothesized that DANCR might also have other target miRNAs that participated in the function of this lncRNA in AS progression.…”

Long Non-coding RNA DANCR in Cancer: Roles, Mechanisms, and Implications

“…DANCR could act as sponges for multiple miRNAs including miR-216a-5p , miR-27a-3p , miR-125b-5p (Yang et al, 2020), miR-140-3p (Wen et al, 2020) and miR-222-3p (Wang X. et al, 2020) in HCC. DANCR could also stabilize PSMD10 (Liu et al, 2020a) and CTNNB1 (Yuan et al, 2016) mRNAs by binding to their 3 UTR region to prevent its degradation by miRNAs.…”

A review on the role of DANCR in the carcinogenesis

“…Both interventions could also inhibit migratory potential and invasiveness of these cells. Mechanistically, DANCR facilitates progression of this cancer through sponging miR-125b-5p and activating MAPK pathway [ 15 ]. DANCR could also contribute in the liver carcinogenesis through sponging miR‐216a‐5p and surging expression of KLF12 [ 16 ].…”

“…DANCR indices ubiquitination of FOXO1 via interacting with FOXO1. PID1 promoted by FOXO1 enhances the chemotherapy sensitivity of GBM cells [ 61 ] miR-125b-5p/MAPK pathway axis HepG2 and Huh-7 cells ∆ DANCR: ↓ migration, invasion [ 15 ] Hepatocellular carcinoma miR-216a-5p/KLF12 axis Huh7, HepG2 and LO2 cells ∆ DANCR: ↓ proliferation, migration, invasion and ↑ apoptosis [ 16 ] miR-222-3p/ ATG7 axis Bel7407, Hep3B, HepG2, Huh7, MHCC97H and LO2 ∆ DANCR: ↓ proliferation and autophagy [ 17 ] PSMD10-IL-6/STAT3 signaling axis HEK-293T, Huh7 and Hep3B DANCR promotes sorafenib resistance via PSMD10-IL-6/STAT3 signaling axis [ 18 ] CTNNB1 HCC cells DANCR is involved in stemness features of hepatocellular carcinoma by derepression of CTNNB1 [ 19 ] miR-27a-3p/ROCK1/LIMK1/COFILIN1 pathway axis MHCC‐97H, Huh7, HCC‐LM3, HepG2, MHCC‐97L, Hep3B, SMMC‐7721 and LO2 ∆ DANCR: ↓ proliferation, and metastasis [ 20 ] β-catenin pathway SMMC-7721 and HCCLM3 ∆ DANCR: ↓ proliferation and metastasis [ 62 ] miR-216a BEAS-2B, NCI-H1299, A549, and NCI-H1975 ∆ DANCR: ↓ proliferation and colony formation [ 10 ] Lung cancer miR-1225-3p/ ErbB2 axis 16HBE, A549, SPCA1, H1299 and H1975 ∆ DANCR: ↓ Migration and Invasion [ 11 ] miR-214-5p/CIZ...…”