LncRNA LINC01134 Contributes to Radioresistance in Hepatocellular Carcinoma by Regulating DNA Damage Response via MAPK Signaling Pathway

Abstract

Hepatocellular carcinoma (HCC) is a highly mortal cancer that could be treated by radiotherapy. DNA damage response (DDR) is a vital factor affecting cancer development after radiotherapy. Long non-coding RNAs (lncRNAs) have been revealed to regulate DNA damage response and repair in cancer cells. Nevertheless, the function of long intergenic non-protein coding RNA 1134 (LINC01134) has not been explored in DDR. In this study, we targeted digging into the function of LINC01134 in DDR and exploring the underlying mechanism in HCC cells. RT-qPCR was employed to measure LINC01134 expression, and we found LINC01134 was significantly upregulated in HCC cells. Functional analysis suggested that LINC01134 depletion attenuated radioresistance of HCC cells by facilitating DNA damage. In vivo assays demonstrated LINC01134 depletion hindered HCC tumor growth. Mechanism assays unveiled LINC01134 sequestered microRNA-342-3p (miR-342-3p) and recruited insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) protein to modulate mitogen-activated protein kinase 1 (MAPK1) expression, consequently activating MAPK signaling pathway. Rescue assays validated the LINC01134/miR-342-3p/MAPK1 axis in the radio-resistant HCC cells. In conclusion, LINC01134 might be identified to be a useful biomarker for the therapy of HCC.

LINC01134 promotes the progression of colorectal cancer through enhancing SLC1A5 mRNA stability

“…Previous studies have shown that LINC01134 was highly expressed in CHOL, COAD, LAML, LIHC [7,8,19], PRAD and READ tissues compared with corresponding normal tissues (Figure S1A). Thus, further analysis was conducted to identify the correlation between LINC01134 and colorectal cancer (CRC) via the online tool GEPIA (http://gepia.cancer-pku.cn/detail.php) [15].…”

“…Recently, LINC01134, a novel lncRNA, was attached to increasing importance in cancers, especially in hepatocellular carcinoma (HCC). It was veri ed that LINC01134 promoted the progression of HCC through facilitating tumors proliferation, migration, epithelial-mesenchymal transition, oxaliplatin resistance, and radioresistance [7][8][9][10]. However, the possible roles and mechanisms of LINC01134 in the occurrence and development of CRC are still largely unclear.…”

Construction and validation of a prognostic signature for mucinous colonic adenocarcinoma based on N7-methylguanosine-related long non-coding RNAs

“…LINC01133 has been shown to play an important role in the occurrence and development of gastric ( 43 ), epithelial ovarian ( 44 ), cervical ( 45 ), and pancreatic cancers ( 46 ). LINC01134 has been proven to be relevant to immune response and metabolism in hepatocellular carcinoma (HCC) and has also been identified as an effective biomarker for HCC treatment ( 47 , 48 ). Furthermore, MHENCR has been found to be a predictor of poor prognosis in CRC patients and a regulator of tumourigenesis through the inhibition of miR-532-p ( 49 ).…”

LINC01134: a pivotal oncogene with promising predictive maker and therapeutic target in hepatocellular carcinoma

“…It has also been implicated in processes such as epithelial-mesenchymal transition (EMT) ( 42 ), immune cell infiltration (specifically T cell migration) ( 52 ), and resistance to chemotherapy and radiotherapy ( 49 – 51 ) in HCC ( Table 1 ). Furthermore, LINC01134 plays a regulatory role in HCC development by influencing key signaling pathways, including the Nuclear Factor Kappa B (NF-κB) inflammatory pathway ( 43 ), the MAPK signaling cascade ( 50 ), and the tumor suppressor p53 pathway ( 45 ), as well as genes involved in tumorigenesis and disease progression ( Table 1 ). These insights are instrumental in comprehending the essential role of LINC01134 in the functional landscape of HCC.…”