Downregulation of LINC00665 suppresses the progression of lung adenocarcinoma via regulating miR-181c-5p/ZIC2 axis

Abstract

Long non-coding RNA (lncRNA) LINC00665 was demonstrated to be upregulated in lung adenocarcinoma (LUAD) and target miR-181c-5p. ZIC2, which is upregulated in LUAD, serves as a putative target of miR-181c-5p. In this study, we aimed to reveal whether LINC00665 regulates miR-181c-5p/ZIC2 axis to promote LUAD progression. The results showed that LINC00665, HOXA1, ZIC2, and HOXA11 levels were increased in LUAD tissues, while miR-181c-5p level was decreased when compared to the adjacent normal tissues. High expression levels of LINC00665, ZIC2, HOXA1 and HOXA11, and low expression of miR-181c-5p were closely linked to poor prognosis of LUAD patients. Knockdown of LINC00665 induced obvious inhibitions in cell viability, clone formation, invasion and tumorigenesis in LUAD cells, whereas miR-181c-5p downregulation significantly neutralized these effects. In addition, downregulation of ZIC2 obviously reversed the enhancements of cell viability, clone formation, invasion and tumorigenesis induced by miR-181c-5p knockdown. In summary, the present study reveals that silencing of LINC00665 suppresses LUAD progression through targeting miR-181c-5p/ZIC2 axis.

[Retracted] Correlation with Spectral CT Imaging Parameters and Occult Lymph Nodes Metastases in Sufferers with Isolated Lung Adenocarcinoma

“…If the disease is not controlled in time, the condition deteriorates rapidly, and the tumor occupies most of the lungs, which will have a great impact on the patient's breathing and pose a great threat to the patient's life [1][2][3][4]. Isolated lung adenocarcinoma is a special type of lung adenocarcinoma, which only manifests as an isolated pulmonary nodule and is prone to occult lymph nodes metastasis, leading to missed diagnosis and misdiagnosis, delaying the best treatment opportunity, and endangering the patient's life [5,6]. At present, an X-ray plain film is the main imaging method for screening and diagnosing chest diseases, but this technology is affected by overlapping, and the resolution is relatively poor [7].…”

The Emerging Roles of LINC00665 in Human Cancers

“…In conclusion, they revealed that LINC00665 upregulated E2F3 expression by acting as a competing endogenous RNA (ceRNA) for miR-138-5p, thereby promoting lung cancer progression ( Wang et al, 2020b ). Similarly, Wei et al (2021) concluded that Linc00665 could bind with miR-181c-5p to upregulate ZIC2, thereby promoting the growth and invasion of lung cancer cells. Huang et al (2021) determined that LINC00665/miR-let-7b/CCNA2 was an essential ceRNA network related to the prognosis of lung cancer.…”

“…Researchers used FISH and qRT-PCR to investigate the subcellular location of LINC00665, and the results revealed that LINC00665 was predominately located in the cytoplasm ( Wang et al, 2021a ). Researchers performed flow cytometry, CCK-8 assays, and transwell assays to evaluate the effects of LINC00665 on lung cancer cell apoptosis, proliferation, migration, and invasion ( Cong et al, 2019 ; Wang et al, 2020b ; Wang et al, 2021a ; Yang et al, 2021a ; Wei et al, 2021 ). The high expression of linc00665 promoted the proliferation, migration, invasion of lung cancer cells in vitro and modulated cell cycle arrest and apoptosis ( Cong et al, 2019 ; Wang et al, 2020b ; Wang et al, 2021a ; Yang et al, 2021a ; Wei et al, 2021 ).…”

“…Yang et al (2021a) revealed that the high expression of LINC00665 was associated with advanced TNM stage, lymph node metastasis, and tumor size. The Kaplan-Meier survival analysis showed that patients with high LINC00665 expression had shorter overall survival and progression-free survival than patients with low LINC00665 expression (Cong et al, 2019;Yang et al, 2021a;Wei et al, 2021). Researchers used FISH and qRT-PCR to investigate the subcellular location of LINC00665, and the results revealed that LINC00665 was predominately located in the cytoplasm (Wang et al, 2021a).…”

The Biological and Molecular Function of LINC00665 in Human Cancers

“…Based on the findings that LINC00665 was primarily distributed in the cytoplasm of NSCLC cells, LINC00665 was found to recruit EZH2 to the CDKN1C promoter region to facilitate the demethylation of histone H3K27 and inhibit CDKN1C transcription. As a ceRNA, LINC00665 could regulate the expression of E2F3, AKR1B10, ZIC2, MYCBP, and CCNA2 by sponging miR-138-5p ( 40 ), miR-98 ( 41 ), miR-181c-5p ( 42 ), miR-195-5p ( 43 ), and miR-let-7b ( 44 ), respectively. LINC00665 also participated in tumor angiogenesis.…”