Linc01614 Regulates the Proliferation, Apoptosis, and Chemotherapy Resistance in Esophageal Squamous Cell Carcinoma by Targeting Mir-4775

Abstract

Background: Esophageal squamous cell carcinoma (ESCC), a widely known esophageal disease, severely affects people's health. Numerous investigations demonstrated that long non-coding RNAs (lncRNAs) performed key jobs inside a wide scope of organic cycles and stand out in malignant growth. Our study planned to investigate the roles and mechanisms of linc01614 in ESCC.
 Methods: A Total of 60 ESCC tissue samples including 30 patients with cisplatin sensitivity and 30 patients with cisplatin resistance, who received DDP-based treatment, were obtained from Zhuhai People's Hospital, Zhuhai City during 2021. These tissues were frozen and saved in a -80 ℃ ultra-low temperature freezer. We performed CCK-8, clone formation, flow cytometry assays to determine the effect of linc01614 on ESCC progression, and explored the specific mechanism of linc01614 in ESCC cell proliferation, apoptosis, and chemotherapy resistance.
 Results: linc01614 expression was upregulated in ESCC tissues and cells compared with non-tumor tissues and human normal esophageal epithelial cells (Het-1A). Knockdown of linc01614 repressed cell expansion, chemotherapy opposition, and advanced cell apoptosis in ESCC. Besides, linc01614 regulated the expression of miR-4775 as a competitive endogenous RNA (ceRNA).
 Conclusion: The linc01614/miR-4775 axis played an important role in ESCC progression and drug resistance, revealing that linc01614 is a promising target in ESCC treatment.

LINC01614 is a promising diagnostic and prognostic marker in HNSC linked to the tumor microenvironment and oncogenic function

“…Accumulating evidence indicated that LINC01614 was abnormally expressed in diverse malignant tumor tissues, including osteosarcoma ( Cai et al, 2021 ), gastric cancer ( Wu et al, 2021 ), glioma ( Wang et al, 2020b ), breast cancer ( Wang et al, 2019a ), and lung cancer ( Sun and Ling, 2019 ), and was closely correlated with clinical pathology indicators and could predict prognosis ( Wang et al, 2020a ; Dong et al, 2021 ). Knockdown of LINC01614 inhibited cell growth, migration, and invasion of THCA and esophageal squamous cell carcinoma ( Wei et al, 2023 ). In BRCA, LINC01614 as a hazard prognosis factor was associated with the HR+/HER2 + molecular subtype ( Li et al, 2023 ).…”

“…It is worth noting that some lncRNAs can serve as early diagnosis biomarkers or prognosis parameters in different human carcinomas ( de Santiago et al, 2021 ). Emerging evidence suggests a compelling correlation between LINC01614 expression and prognostic outcomes of lung cancer ( Liu et al, 2022 ), gastric cancer ( Chen et al, 2021 ), and ESCA prognosis ( Wei et al, 2023 ). LINC01614 was relevant to the HR+/HER2 + breast cancer molecular subtype and accelerated breast cancer cell proliferation and migration by TGF-β and focal adhesion kinase (FAK) signaling ( Vishnubalaji et al, 2019 ).…”

Roles of long non‑coding RNAs in esophageal cell squamous carcinoma (Review)

“…Furthermore, after cisplatin treatment, lncRNA non-coding repressor of NFAT was upregulated, contributing to cisplatin resistance by downregulating miR-31 in KYSE510 ( 116 ). Another study showed that Linc01614/miR-4775 enhanced proliferation and cisplatin resistance in EC9706 and KYSE30 cells, while inhibiting cell apoptosis and promoting CDX growth in EC9706 ( 117 ). In addition, lncRNA HCP5 inhibited UTP3 small subunit processome component ubiquitination and degradation, leading to the recruitment of c-MYC to activate vesicle associated membrane protein 3 expression and inhibited caspase-dependent apoptosis, ultimately resulting in cisplatin resistance in CDX (KYSE150) ( 118 ).…”