HAND2-AS1 inhibits invasion and metastasis of cervical cancer cells via microRNA-330-5p-mediated LDOC1

Abstract

Background: Cervical cancer is a serious disease with complicated pathogenesis and thus there is an urgent need to find novel targets for the treatment. Recently, long non-coding RNAs (lncRNAs) have emerged as critical factors in tumorigenesis. In this study, we aimed to investigate the mechanism of HAND2 antisense RNA 1 (HAND2-AS1) on the invasion and metastasis of cervical cancer cells. Methods: The expression patterns of HAND2-AS1, microRNA-330-5p (miR-330-5p) and leucine zipper down-regulated in cancer 1 (LDOC1) in cervical cancer were characterized by RT-qPCR and western blot analysis. Dual luciferase reporter assay and RIP were applied to verify relationship between HAND2-AS1, miR-330-5p and LDOC1. Fluorescence in situ hybridization (FISH) was used to detect the subcellular localization of HAND2-AS1. Besides, viability, invasion and migration ability of HeLa cells were investigated by cell counting kit-8 (CCK-8) and Transwell assays respectively. Hematoxylin-eosin staining was performed for lymph node metastasis detection. In addition, the tumor growth in nude mice was evaluated. Results: Low expression of HAND2-AS1 and LDOC1, and high expression of miR-330-5p were detected in cervical cancer tissues and cells. It was found that binding of HAND2-AS1 to miR-330-5p results in upregulation of LDOC1 expression. Also, overexpressed HAND2-AS1 and LDOC1 or down-regulated miR-330-5p inhibited expression of proliferation-associated proteins Ki-67, PCNA, migration-associated proteins N-cad and invasion-related proteins MMP-2, MMP-9 as well as lymph node metastasis. Moreover, HAND2-AS1 inhibited tumor formation and lymph node metastasis by binding to miR-330-5p in vivo. Conclusion: HAND2-AS1 promotes LDOC1 expression by competitively binding to miR-330-5p and consequently inhibiting cervical cancer cell invasion and metastasis. This could facilitate development of therapeutic strategies against cervical cancer.

Mesenchymal stem cell-originated exosomal lncRNA HAND2-AS1 impairs rheumatoid arthritis fibroblast-like synoviocyte activation through miR-143-3p/TNFAIP3/NF-κB pathway

“…Exosomes are small spherical packages, which possess the physical properties of artificial nanoparticles and additional advantages such as excellent biocompatibility, biodegradability, and sequence programmability, and are ideal drug delivery carriers [33]. In the current study, we generated hMSC-HAND2-AS1-Exos (exosomes derived from HAND2-AS1-overexpressing hMSCs); after the co-incubation of RA-FLSs with hMSC-HAND2-AS1-Exos, HAND2-AS1 Previous studies have shown that HAND2-AS1 can perform a suppressive role in tumor progression by serving as a sponge of miRNAs [11,12]. Emerging evidence has revealed that the novel regulatory network of lncRNAs-miRNAs-mRNAs plays a significant role in the pathophysiological processes of many diseases, including RA [34,35].…”

“…Previous studies have shown that HAND2-AS1 can perform a suppressive role in tumor progression by serving as a sponge of miRNAs [ 11 , 12 ]. Emerging evidence has revealed that the novel regulatory network of lncRNAs-miRNAs-mRNAs plays a significant role in the pathophysiological processes of many diseases, including RA [ 34 , 35 ].…”

“…LncRNAs have been corroborated to have significant roles in complex human pathologies through regulating cell biological processes, such as proliferation, apoptosis, metastasis, metabolism, and inflammation [6][7][8], and the dysregulation of lncRNAs is associated with the physiological status and pathological progression of many diseases, including RA [9,10]. LncRNA heart and neural crest derivatives expressed 2antisense RNA 1 (HAND2-AS1) is a well-recognized tumor suppressor in different types of cancer [11][12][13]. Previous study found that the level of HAND2-AS1 was low in RA-FLSs, suggesting that abnormal HAND2-AS1 expression might be involved in synovial aggression and joint destruction in RA [14].…”

Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Cervical Cancer

“…E2F4 is also overexpressed in cervical cancer lesions. However, a recent study pointed to evidence that HAND2-AS1 recruits the transcription factor E2F4 to the C16orf74 promoter region and down-regulates C16orf74 expression to suppress cervical cancer development [55]. Although there was no signi cant upor down-regulation of E2F4 expression levels in CC, further studies on the role of E2F4 in CC are needed, considering the little evidence available.…”

Ginsenoside Rh2 inhibits HeLa cell energy metabolism and induces apoptosis by upregulating voltage‑dependent anion channel 1

“…Cervical cancer is the fourth most common gynecological malignant tumor that affects females, and results in ~57,000 new cases annually with 311,000 deaths worldwide ( 1 , 2 ). In China, the incidence of cervical cancer has increased rapidly over the past 20 years ( 3 ).…”