The Expression and Clinical Significance of Non-coding RNA in Cervical Cancer
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摘要:
目的 分析非编码RNA 长链非编码RNA（LINC00982）及微小RNA（hsa-miR-1246）在子宫颈癌组织中的表达情况，旨在为宫颈癌的诊断提供新的生物标志物和潜在的治疗靶点。 方法 收集云南大学附属医院2021年1月至2021年10月收治的21例因子宫肌瘤等良性病变行全子宫切除术患者的正常宫颈组织样本（对照组）和43例经病理学诊断为子宫颈癌患者的宫颈癌组织样本（实验组），运用实时荧光定量PCR（RT-qPCR）检测并比较2组间LINC00982及hsa-miR-1246的表达情况。 结果 （1）与人正常子宫颈组织相比，子宫颈癌组织中LINC00982-1/2的表达下调（P < 0.05），而hsa-miR-1246表达上调（P < 0.05）；（2）高分化宫颈癌组织中LINC00982-1/2及hsa-miR-1246的表达量低于中低分化宫颈癌组织（P < 0.05）；（3）Ⅲ/Ⅳ期人宫颈癌组织中LINC00982-1/2及hsa-miR-1246的表达量高于Ⅰ/Ⅱ期（P < 0.05）；（4）腺癌组织中LINC00982-1的表达量低于鳞状细胞癌（P < 0.05），但腺癌与鳞状细胞癌中LINC00982-2两者比较，差异无统计学意义（P > 0.05），而hsa-miR-1246的表达量则高于鳞状细胞癌（P < 0.05）；（5）LINC00982-1/2表达量随SCCA的增高而下降（P < 0.05），而hsa-miR-1246表达量随SCCA的增高而增高；（6）肿瘤直径 > 4 cm的组织中，LINC00982-1/2及hsa-miR-1246的表达量高于肿瘤直径≤4 cm者。 结论 LINC00982在宫颈癌组织中低表达；hsa-miR-1246在宫颈癌组织中高表达；且子宫颈癌组织中LINC00982-1/2及hsa-miR-1246表达与组织分化程度、病理分期、病理类型、SCCA的高低及肿瘤直径密切相关。 Abstract:Objective To analyze the expression of long non-coding RNA （LINC00982） and microrNA （hsa-miR-1246） in cervical cancer tissues, so as to provide a new biomarker for the diagnosis of cervical cancer and a potential and effective therapeutic target for its treatment. Methods The normal cervical tissue samples （as the control group） were collected from 21 patients undergoing the total hysterectomy for benign lesions such as uterine fibroids and the cervical cancer tissue samples （as the experimental group） were collected from 39 patients diagnosed as cervical cancer by pathology. All the patients above were admitted to the Affiliated Hospital of Yunnan University from January 2021 to October 2021. The expressions of LINC00982 and miR-1246 were detected and compared between these two groups by real-time fluorescence quantitative PCR （RT-QPCR）. Results （1） Compared with the normal human cervical tissues, the expression of LINC00982-1/2 was down-regulated in cervical cancer tissues （P < 0.05）, while the expression of hsa-miR-1246 was up-regulated （P < 0.05）; （2）The expression levels of LINC00982-1/2 and miR-1246 in highly differentiated cervical cancer tissues were lower than those in medium and low differentiated cervical cancer tissues （P < 0.05）; （3） The expression levels of LINC00982-1/2 and hsa-miR-1246 in stage Ⅲ/Ⅳ of the cervical carcinoma were higher than those in stage Ⅰ/Ⅱ （P < 0.05）. （4） The expression level of LINC00982-1 in adenocarcinoma tissues was lower than that in squamous cell carcinoma （P < 0.05）, but there was no significant difference between adenocarcinoma and squamous cell carcinoma （P > 0.05）, while the expression of hsa-mir-1246 was higher than that in squamous cell carcinoma （P < 0.05）; （5） The expression of LINC00982-1/2 decreased with the increase of SCCA （P < 0.05）, while the expression of hsa-miR-1246 increased with the increase of SCCA; （6） The expression levels of LINC00982-1/2 and hsa-miR-1246 in tissues with the tumor diameter > 4 cm were higher than those with tumor diameter ≤4 cm. Conclusion LINC00982 is low expressed in cervical cancer tissues while hsa-miR-1246 is highly expressed in cervical cancer tissues. Furthermore, the expressions of LINC00982-1/2 and hsa-miR-1246 in cervical cancer tissues are closely related to the degree of tissue differentiation, pathological stage, pathological type, SCCA level and tumor diameter. -
Key words:
- Cervical cancer /
- Long non-coding RNA /
- micro RNA
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图 1 LINC00982剪切体1及LINC00982剪切体2在正常子宫颈及子宫颈癌组织中的表达情况
A：LINC00982剪切体1在正常子宫颈及子宫颈癌组织中的表达情况；B： LINC00982剪切体2在正常子宫颈及子宫颈癌组织中的表达情况。 与对照组比较，#P < 0.05。
Figure 1. Expression of LINC00982-1 and LINC00982-2in normal cervical and cervical carcinoma
图 2 hsa-miR-1246在正常宫颈及子宫颈癌组织中的表达情况
与对照组比较，*P < 0.05 。
Figure 2. expression of hsa-miR-1246 in normal cervical and cervical carcinoma
图 3 LINC00982剪切体1和LINC00982剪切体2在人正常宫颈及不同分化程度的宫颈癌组织中的表达变化
A：LINC00982剪切体1在人正常宫颈及不同分化程度的宫颈癌组织中的表达变化；B：LINC00982剪切体2在人正常宫颈及不同分化程度的宫颈癌组织中的表达变化。 与对照组比较，*P < 0.05；与低、中分化组比较，#P < 0.05。
Figure 3. Expression of LINC00982-1 and LINC00982-2 in normal cervical and cervical cancer tissues with different degrees of differentiation
图 4 hsa-miR-1246在人正常宫颈及不同分化程度的宫颈癌组织中的表达变化
与对照组比较，*P < 0.05 ；与低、中分化组比较，#P < 0.05。
Figure 4. Expression of hsa-miR-1246 in normal cervical and cervical cancer tissues with different degrees of differentiation.
图 5 LINC00982剪切体1和LINC00982剪切体2在人正常宫颈及不同分期的宫颈癌组织中的表达变化
A：LINC00982剪切体1和LINC00982剪切体2在人正常宫颈及不同分期的宫颈癌组织中的表达变化；B：LINC00982剪切体2在人正常宫颈及不同分期的宫颈癌组织中的表达变化。 与对照组比较，*P < 0.05；与Ⅰ/Ⅱ期比较，#P < 0.05。
Figure 5. Expression of LINC00982-1 and LINC00982-2 in normal cervix and cervical cancer tissues of different stages
图 6 hsa-miR-1246在人正常宫颈及不同分期的宫颈癌组织中的表达变化
与对照组比较，*P < 0.05；与Ⅰ/Ⅱ期比较，#P < 0.05。
Figure 6. Expression of hsa-miR-1246 in normal cervix and cervical cancer tissues of different stages.
图 7 LINC00982剪切体1和剪切体2在正常子宫颈及子宫颈癌组织不同病理类型中的表达变化
A：LINC00982剪切体1在正常子宫颈及子宫颈癌组织不同病理类型中的表达变化；B：LINC00982剪切体2在正常子宫颈及子宫颈癌组织不同病理类型中的表达变化。 与对照组比较，*P < 0.05，与鳞状细胞癌组比较，# P < 0.05。
Figure 7. Expression of LINC00982-1 and LINC00982-2 in different pathological types of normal cervix and cervical cancer tissues.
图 8 hsa-miR-1246在正常子宫颈及子宫颈癌组织不同病理类型中的表达变化
与对照组比较，*P < 0.05，与鳞状细胞癌组比较，#P < 0.05。
Figure 8. expression of hsa-miR-1246 in different pathological types of normal cervix and cervical cancer tissues.
图 9 LINC00982剪切体1和LINC00982剪切体2在正常人子宫颈及子宫颈癌组织不同SCCA表达量
A：LINC00982-1在正常人子宫颈及子宫颈癌组织不同SCCA表达量；B：LINC00982-2在正常人子宫颈及子宫颈癌组织不同SCCA表达量。 与正常宫颈组比较，*P < 0.05；与SCCA（ < 1.5 ng/mL）组比较，#P < 0.05。
Figure 9. Expression of LINC00982-1 and LINC00982-2 in normal cervix and cervical cancer tissues with different SCCA levels
图 10 hsa-miR-1246在正常人子宫颈及子宫颈癌组织不同SCCA表达量
与对照组比较，*P < 0.05 ；与SCCA（ < 1.5 ng/mL）组比较，#P < 0.05。
Figure 10. Expression of hsa-miR-1246 in normal cervix and cervical cancer tissues with different SCCA levels
图 11 LINC00982剪切体1和LINC00982剪切体2在正常人子宫颈及子宫颈癌不同肿瘤大小中的表达变化
A：LINC00982剪切体1和LINC00982剪切体2在正常人子宫颈及子宫颈癌不同肿瘤大小中的表达变化图；B：LINC00982剪切体2在正常人子宫颈及子宫颈癌不同肿瘤大小中的表达变化。 与对照组比较，*P < 0.05；与≤4 cm颈肿瘤组织组比较，#P < 0.05。
Figure 11. Expression of LINC00982-1 and LINC00982-2 in the normal cervix and different tumor sizes of cervical cancer
图 12 hsa-miR-1246在正常人子宫颈及子宫颈癌不同肿瘤大小中的表达变化
与正常宫颈组比较，*P < 0.05；与≤4 cm颈肿瘤组织组比较，#P < 0.05。
Figure 12. Expression of hsa-miR-1246 in the normal cervix and different tumor sizes of cervical cancer.
表 1 实时荧光定量PCR引物序列
Table 1. The sequence of RT-PCR primers
Primer 序列 LINC00982-1：F 5′-CCTGGCAGCAACGAAAATGG-3′ LINC00982-1：R 5′-TTTGCAAGCCGAGTCTGGAT-3′ LINC00982-2：F 5′-TGGCACCAGAGATTGAGACTG-3′ LINC00982-2：R 5′-CCGCACACGAGTAGGAGTCGT-3′ GAPDH：F 5′-GAGCGAGATCCCTCCAAAAT-3′ GAPDH：R 5′-GCTGTTGTCATACTTCTCATCG-3′ hsa-miR-1246 5′-AATGGATTTTTGGAGCAGG-3′ U6 5′-CTCGCTTCGGCAGCACA-3′ 
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表 2 LINC00982、hsa-miR-1246表达量（
$\bar x \pm s $ ）Table 2. Expression levels of LINC00982 and hsa-miR-1246 （
$\bar x \pm s $ ）组别 n LINC00982-1 LINC00982-2 hsa-miR-1246 正常宫颈组 21 1.00 ± 0.123 1.00 ± 0.145 1.00 ± 0.2883 宫颈癌组 43 0.6561 ± 0.2487 0.1173 ± 0.1391 2.0500 ± 0.2345 F 18.88 334.3 154 P 0.0029* 0.0080* 0.0047* 与正常宫颈组比较，*P < 0.05。
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表 3 LINC00982、hsa-miR-1246表达量（
$\bar x \pm s $ ）Table 3. Expression levels of LINC00982 and hsa-miR-1246 （
$\bar x \pm s $ ）组别 n LINC00982-1 LINC00982-2 hsa-miR-1246 正常宫颈组 21 1.00 ± 0.123 1.00 ± 0.145 1.00 ± 0.2883 低、中分化 30 0.6142 ± 0.1887* 0.1751 ± 0.1537* 1.8950 ± 0.5421* 高分化 13 0.4234 ± 0.1452*# 0.0037 ± 0.0045*# 1.561 ± 1.0107*# F 59.63 306.5 13.46 P 0.0012 0.0001 0.0001 与正常宫颈组比较，*P < 0.05；与低、中分化组比较，#P < 0.05。
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表 4 LINC00982、hsa-miR-1246表达量（
$\bar x \pm s $ ）Table 4. Expression levels of LINC00982 and hsa-miR-1246 （
$\bar x \pm s $ ）组别 n LINC00982-1 LINC00982-2 hsa-miR-1246 正常宫颈组 21 1.00 ± 0.123 1.00 ± 0.145 1.00 ± 0.2883 Ⅰ/Ⅱ 28 0.0318 ± 0.0528* 0.0044 ± 0.0023* 1.314 ± 0.1513* Ⅲ/Ⅳ 15 1.3420 ± 0.1155*# 0.2796 ± 0.2371*# 3.365 ± 1.1452*# F 1105 307.1 82.81 P 0.0002 0.0001 0.0001 与正常宫颈组比较，*P < 0.05；与Ⅰ/Ⅱ期比较，#P < 0.05。
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表 5 LINC00982、hsa-miR-1246表达量（
$\bar x \pm s $ ）Table 5. Expression levels of LINC00982 and hsa-miR-1246（
$\bar x \pm s $ ）组别 n LINC00982-1 LINC00982-2 hsa-miR-1246 正常宫颈组 21 1.00 ± 0.123 1.00 ± 0.145 1.00 ± 0.2883 SSC 38 0.4373 ± 0.0529* 0.0053 ± 0.0052* 1.436 ± 0.2348* ADS 5 0.2022 ± 0.1151*# 0.0172 ± 0.0145*# 4.455 ± 0.3146*# F 346.6 995.5 808.9 P 0.0002 0.0001 0.0004 与正常宫颈组比较，*P < 0.05；与鳞状细胞癌组比较，#P < 0.05。
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表 6 LINC00982、has-miR-1246表达量（
$\bar x \pm s $ ）Table 6. Expression levels of LINC00982 and hsa-miR-1246（
$\bar x \pm s $ ）组别 n LINC00982-1 LINC00982-2 hsa-miR-1246 正常宫颈组 21 1.00 ± 0.123 1.00 ± 0.145 1.00 ± 0.2883 SSCA（ < 1.5 ng/mL） 28 0.5360 ± 0.2155* 0.0078 ± 0.0022* 1.425 ± 0.1545* SCCA（≥1.5 ng/mL） 15 0.2822 ± 0.1946*# 0.0057 ± 0.0019*# 1.66 ± 0.1446*# F 72.16 273.1 48.88 P 0.0391 0.0001 0.0025 与正常宫颈组比较，*P < 0.05；与SCCA（ < 1.5 ng/mL）组比较，#P < 0.05。
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表 7 LINC00982、has-miR-1246表达量（
$\bar x \pm s $ ）Table 7. Expression levels of LINC00982 and hsa-miR-1246（
$\bar x \pm s $ ）组别 n LINC00982-1 LINC00982-2 hsa-miR-1246 正常宫颈组 21 1.00 ± 0.123 1.00 ± 0.145 1.00 ± 0.2883 ≤4 cm 12 0.4156 ± 0.1546* 0.0037 ± 0.0040* 1.509 ± 0.1376* > 4 31 0.5814 ± 0.1398*# 0.0335 ± 0.0070*# 2.201 ± 0.1795*# F 87.04 969.3 198.6 P 0.0007 0.0001 0.0108 与正常宫颈组比较，*P < 0.05；与≤4 cm颈肿瘤组织组比较，#P < 0.05。
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