RP11-462C24.1 suppresses proliferation and invasion of colorectal carcinoma cells by regulating HSP70 through PI3K/AKT s
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RESEARCH ARTICLE
RP11‑462C24.1 suppresses proliferation and invasion of colorectal carcinoma cells by regulating HSP70 through PI3K/AKT signaling pathway Haiqing Zhang1 · Guangjun Zhang1 · Haijun Liu1 · Yuanzhou Shan1 · Xueli Zhang1 Received: 8 May 2020 / Accepted: 1 September 2020 © Japan Human Cell Society 2020
Abstract Colorectal cancer (CRC) is the third leading cause of cancer-related death around the world. In this study, we investigated the roles of LncRNA RP11-462C24.1 in CRC. The expressions of RP11-462C24.1 in CRC tissues and cells were measured. Then, the effects of RP11-462C24.1 on CRC proliferation, cell cycle, apoptosis, and invasion were evaluated both in vivo and in vitro; Last, the underlying mechanisms of concerning the signaling pathway regulated by RP11-462C24.1 was determined. From the results, we found that RP11-462C24.1 was significantly decreased in CRC tumor tissues and the CRC cell lines, which were most significant in SW480 and HT-29 cell lines; moreover, transient overexpression of RP11-462C24.1 suppressed the growth and migration while promoted apoptosis of SW480 and HT-29 cells, while knockdown of RP11462C24.1 has shown the opposite effects; RP11-462C24.1 may also inhibit the growth of CRC tumors in xenograft mice models; additionally, 70 kD heat shock proteins (HSP70) has been identified as one of the most significantly deferentially expressed genes by RNA-seq, and we further confirmed that RP11-462C24.1 may affect the growth and metathesis of CRC cells via regulating HSP70 and PI3K/AKT signaling pathway. In summary, these results indicated that RP11-462C24 may function as a tumor suppressor in the development of CRC. Keywords RP11-462C24.1 · CRC · LncRNA · HSP70
Introduction Colorectal cancer (CRC) is the most common gastrointestinal cancer (incidence number > 900,000/year), and it is the NO.1 cause of cancer-induced motility worldwide [1–3]. According to the results of previous reports, CRC may derive from a series of abnormal genetic and molecular alterations in colon epithelial cells, leading to the uncontrolled growth of the cancer cells [4, 5]. Currently, surgery, chemotherapy, and radiotherapy were the most commonly used methods for the treatment of CRC; however, none of the current anti-CRC methods have achieved the desired * Xueli Zhang [email protected] Haiqing Zhang [email protected] 1
Department of General Surgery, Affiliated Fengxian Hospital, The Third School of Clinical Medicine, Southern Medical University, 6600 Nanfeng Highway, Shanghai 201499, China
therapeutic efficacy, and the long-term prognosis of the CRC patients is still poor [6, 7]. Therefore, identifying novel diagnostic biomarkers and novel therapeutic targets for the early diagnosis and treatment of CRC is in high demand. Long non-coding RNAs (LncRNAs) belongs to the noncoding RNA family. The length of LncRNAs are longer than 200 nucleotides, and some of the LncRNAs can reach to kilobases in length [8, 9]. Results of previous studies suggested that LncRNAs may participate in multiple
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